The team, led by Marios G. Krokidis, combined AlphaFold-based structure prediction, the disorder-focused FuzPred algorithm, and HADDOCK molecular docking simulations to compare wild-type FUS with three mutant variants: G156E, R234L, and R521C. Each mutation sits in a different functional region of the 526-residue protein, which is largely built from intrinsically disordered regions — stretches that never settle into one rigid shape but instead constantly sample many conformations. FUS uses this flexibility to bind RNA, regulate transcription, participate in DNA damage repair, and shuttle between the nucleus and cytoplasm.

The structural comparison revealed that none of the mutations causes a dramatic collapse of the protein’s folded domains. Global backbone deviations, measured on high-confidence residues, ranged from about 5.5 angstroms for R234L to roughly 15.4 angstroms for R521C, but these values mostly reflect changes in how the intact folded domains — such as the RNA recognition motif and zinc finger — are oriented relative to one another through flexible linkers, not classical misfolding. The mutations themselves all fall in regions that AlphaFold flags as low-confidence, consistent with their intrinsically disordered character.

More telling were the local measurements. Solvent-accessible surface area calculations showed that all three mutants expose additional surface to the aqueous environment, with G156E and R521C producing the largest increases — 104.24 and 108.44 square angstroms respectively — and strongly negative hydrophobicity-weighted values, indicating that hydrophobic patches are being pushed into contact with water. The authors suggest this creates a thermodynamic drive to bury those patches through aberrant intermolecular aggregation, a route that could push FUS away from its native dynamic state and toward pathological solid-like phase transitions.

The FuzPred analysis sharpened the picture. For each residue, the algorithm estimates the probability of a disorder-to-order transition upon binding (pDO), the probability of remaining disordered (pDD), and the multiplicity of binding modes (MBM), which captures how many different interaction geometries a region can explore. When the researchers subtracted the wild-type profile from each mutant’s, the global differences were tiny — but the local changes within ten residues of each mutation site were clearly visible. All three mutations reduced local pDD and increased local MBM, suggesting a loss of the protein’s healthy, fuzzy binding behavior and a drift toward less coordinated, more promiscuous interaction patterns.

The docking simulations then connected these local disorder changes to concrete functional consequences. For R521C, which sits in the C-terminal proline-tyrosine nuclear localization signal, the team docked the NLS peptide against Transportin-1, the nuclear import receptor that normally carries FUS into the nucleus. The wild-type peptide bound with a HADDOCK score of −87.8 ± 3.4 kcal/mol, while the R521C mutant scored −79.5 ± 3.6 — weaker, despite actually presenting a slightly larger buried surface area. The energy breakdown showed the mutant’s electrostatic contribution dropped sharply, from −382.9 to −264.5 kcal/mol, indicating that replacing a positively charged arginine with cysteine undermines the charge complementarity that drives recognition. This aligns with earlier experimental and computational work showing that R521C reduces Transportin-1 affinity and causes FUS to accumulate in the cytoplasm, a major pathogenic step in ALS.

For G156E, which lies just upstream of the RGG1 RNA-binding domain, the team docked a 60-residue peptide against a 23-nucleotide RNA fragment. The wild-type complex achieved a HADDOCK score of −74.7 ± 1.6 kcal/mol with a buried surface of roughly 1,736 square angstroms, reflecting the multivalent contacts typical of RGG-mediated RNA recognition. The G156E mutant scored −61.6 ± 5.7, with a smaller interface of about 1,401 square angstroms. The authors attribute this to the added glutamate’s negative charge sitting close to the RNA phosphate backbone, increasing electrostatic repulsion and weakening the interaction. Because RGG domains help drive RNA-dependent phase separation and the formation of ribonucleoprotein granules, weakening these contacts could destabilize normal condensates and promote the misregulated RNA metabolism seen in ALS.

R234L, located in the intrinsically disordered RGG2 domain, could not be docked in the conventional sense because no experimentally determined FUS–RNA complex involving that region exists, and standard docking platforms require well-defined structural templates. Instead, the researchers interpreted its effects through the disorder analysis, which showed a local reduction in pDD — a loss of the native, functional flexibility that RGG domains rely on for multivalent RNA recognition. Removing an arginine from this positively charged motif would be expected to diminish both electrostatic attraction and cation–π interactions with RNA, consistent with the mutation’s association with disrupted RNA metabolism.

Taken together, the findings support a view of FUS-related ALS in which pathogenicity arises not from wholesale misfolding but from localized rearrangements in intrinsic disorder, binding versatility, and molecular recognition. Each mutation prunes a different functional modality — R521C compromises nuclear import, G156E weakens RNA binding, R234L erodes RGG2-mediated interactions — yet all three converge on the same cellular outcome: impaired nucleocytoplasmic distribution, altered stress granule behavior, and a tendency toward pathological aggregation. The authors caution that AlphaFold-derived models of intrinsically disordered regions should be treated as plausible conformational hypotheses rather than definitive structures, and they propose extending the approach with molecular dynamics simulations, multiple RNA sequence contexts, and integration with experimental data from NMR, cross-linking, and cellular localization assays. The same computational framework could also be applied to other disordered ALS proteins such as TDP-43 and hnRNPA1, offering a route toward therapies that restore protein localization and RNA homeostasis rather than simply blocking aggregation.

Subject of Research: Computational analysis of how ALS-associated FUS mutations alter conformational dynamics, intrinsic disorder, and molecular interactions

Article Title: ALS-associated FUS mutations induce site-specific alterations in conformational dynamics and molecular interactions

Article References: Amourgianos, C., Exarchos, T. P., Vlamos, P., & Krokidis, M. G. (2026). ALS-associated FUS mutations induce site-specific alterations in conformational dynamics and molecular interactions. Frontiers in Chemical Biology, 5, Article 1851848. https://doi.org/10.3389/fchbi.2026.1851848

Image Credits: AI Generated

DOI: 10.3389/fchbi.2026.1851848

Keywords: ALS, FUS, intrinsically disordered proteins, AlphaFold, FuzPred, HADDOCK, molecular docking, RNA binding, nuclear import, Transportin-1, phase separation, neurodegeneration

The stakes of this research are enormous. Genome organization is intimately connected to essential cellular functions such as gene expression, DNA replication, and DNA repair. Enhancers, the distal regulatory elements that boost gene activity, may lie millions of DNA letters away from the genes they control along the linear chromosome, yet they must physically find and contact their targets within the crowded nuclear space. Understanding how the chromatin fiber brings the right pieces together requires more than biology alone; it requires quantitative models in which chromosomes are treated as polymer chains and proteins as interacting particles whose collective behavior can be simulated, perturbed, and compared against experimental data from microscopy and chromosome-conformation assays.

The first pillar of the framework discussed by Fontana and Chiariello is phase separation, the same process that causes oil to bead up in water, here operating on proteins inside the nucleus. Many regulatory proteins carry intrinsically disordered regions that allow them to interact with copies of themselves, forming stable condensates. Well-studied examples include Mediator and RNA polymerase II, which cluster together at active genes, as well as coactivators that assemble at super-enhancers and transcription factors whose activation domains can condense to drive gene expression. At larger scales, phase separation helps build Cajal bodies and the nucleolus, a multi-phase structure assembled from distinct molecular species of proteins and RNA. Crucially, when the phase-separation properties of these proteins go wrong, the result can be disease, ranging from rare genetic disorders involving nucleolar dysfunction to cancer driven by aberrant condensates.

To capture this phenomenon computationally, theorists have built models in which chromatin is represented as a polymer and proteins are represented as particles that bind to it. Some of the simplest versions include only polymer-protein interactions, leaving out direct protein-protein attraction. Even so, these bridging models give rise to what is known as polymer-polymer phase separation, in which the polymer itself nucleates condensates of bound proteins that then glue distant chromatin segments together. Despite their minimalism, such models have successfully reconstructed the three-dimensional structures of real genomic regions, described chromatin remodeling across different cell types, and even tracked how genome architecture is rearranged following viral infections, including SARS-CoV-2.

More realistic systems require explicit protein-protein interactions alongside chromatin-protein affinity, and, in the most complete versions, loop extrusion as well. In loop extrusion, molecular motors of the cohesin or condensin families slide along the chromatin fiber, enlarging DNA loops until they are halted at anchor points, often corresponding to binding sites of the architectural protein CTCF. Single-molecule imaging has now captured this process in real time, and computational studies show that extrusion contributes to global chromosome condensation during mitosis as well as to the local loops and domains that organize the interphase genome. When all these ingredients coexist, the behavior of the system is governed by a set of control parameters, including protein concentration, self-interaction affinity, chromatin affinity, and motor density and processivity, and the resulting equilibrium states fall into complex phase diagrams reminiscent of those studied in condensed matter physics.

One of the most striking predictions to emerge from large-scale molecular dynamics simulations concerns a scenario now called polymer-assisted condensation, or PAC. Simulations revealed that phase-separated condensates can arise in two distinct ways: either spontaneously through strong protein-protein affinity, independently of the polymer, or in a polymer-assisted route in which protein-protein attraction alone is too weak to drive condensation, but binding to chromatin concentrates the proteins enough to tip the system over the threshold. This second mechanism, first predicted computationally and later explored theoretically, has been proposed as a potentially general principle of chromatin organization, with implications for heterochromatin formation and epigenetic memory.

The power of the integrated approach was demonstrated in recent work on PHF13, a protein that binds chromatin enriched with the histone methylation marks H3K4me3 and H3K27me3 and can also self-associate through specific N-terminal sub-domains. Molecular dynamics simulations showed that when both chromatin-protein and protein-protein interactions were enabled at sufficient PHF13 concentration, the modeled polymer collapsed into a compact, roughly spherical globule decorated with PHF13 clusters, mirroring microscopy images of interphase cells overexpressing PHF13, in which chromosomes condense into rounded structures. When the self-interaction domains were disabled in silico, compaction was reduced and condensation disappeared, exactly matching the behavior of engineered PHF13 variants lacking those domains in living cells. The close agreement between simulation and experiment provides a compelling validation of the physics-based framework.

The same modeling philosophy is now being applied to disease. The chimeric protein NUP98-HOXA9, an oncofusion associated with leukemia, can undergo phase separation and bind chromatin, promoting the formation of aberrant loops that bring oncogenes such as PBX3 into contact with distant regulatory elements. Models of the relevant genomic regions accurately recapitulated the aberrant looping patterns observed in experimental Hi-C contact maps from human cells and in single-molecule mobility measurements, while also capturing the interplay between phase separation and loop extrusion that underlies the pathological rewiring. Because altered phase separation has been implicated in cancers and rare genetic diseases, such models offer a route to understanding how molecular-scale misfolding translates into gene misregulation.

The third pillar of the framework concerns the nuclear envelope. The nuclear lamina, a protein network embedded in the inner membrane, adsorbs peripheral chromatin, spatially segregating specific genomic regions from the nuclear interior and repressing their activity. Computational models represent the lamina as an adsorbing membrane that attracts or sterically excludes chromatin segments, with interactions parameterized from DamID profiles that quantify locus-specific lamina association. When loop extrusion and lamina adsorption are combined in a single simulation, the framework accurately reproduces the organization of peripheral loci such as the mouse Sox9 and Kcnj2 region, and tuning chromatin-lamina affinity allows different degrees of peripheral association and distinct cell populations to be described. Simulations of genomic editing, including deletion of CTCF boundary elements, quantitatively matched experimental outcomes, establishing a link between loop extrusion and lamina association even though the two processes act independently.

Fontana and Chiariello conclude that the great advantage of these physics-based models is their versatility: phase separation, loop extrusion, and membrane adsorption can be combined within a single computational framework to describe increasingly detailed biological contexts, at the cost of larger parameter spaces and more complex phase diagrams that molecular dynamics simulations are well suited to explore. Looking forward, the authors point to promising extensions, including modeling pathogenic protein variants, the chromatin changes of ageing, and the architectural disruptions induced by external pathogens such as viruses. As genome-wide datasets grow richer and simulations grow faster, the dream of predicting, and perhaps one day correcting, the physical misfolding events behind human disease moves steadily closer to reality.

Subject of Research: Physics-based computational modeling of chromatin 3D organization through phase separation, loop extrusion, and nuclear lamina adsorption

Article Title: On the physics of chromatin molecular complex: from phase-separation to membrane adsorption

Article References: Fontana, A., & Chiariello, A. M. (2026). On the physics of chromatin molecular complex: from phase-separation to membrane adsorption. Frontiers in Molecular Biosciences, 13, Article 1951961. https://doi.org/10.3389/fmolb.2026.1951961

Image Credits: AI Generated

DOI: 10.3389/fmolb.2026.1951961

Keywords: chromatin, 3D genome organization, phase separation, loop extrusion, polymer physics, nuclear lamina, molecular dynamics, gene regulation, biomolecular condensates, CTCF, cohesin, leukemia

Recent experiments have established that condensate interfaces are not passive bystanders in amyloid formation. In condensates formed by the low-complexity domain of the RNA-binding protein hnRNPA1, and in droplets of the ALS-linked protein FUS, fibril formation is strongly enhanced at the droplet surface rather than in the interior. Other condensate systems suppress aggregation by sequestering proteins inside, or redirect it by altering the structural polymorphism of amyloid-forming proteins like Tau and Aβ. What has remained unclear is which molecular and physical variables select among these outcomes. The new work tackles this question with a purpose-built simulation framework called flux-driven molecular dynamics, or FD-MD, which allows the researchers to independently tune chain architecture, chain rigidity, and the transport of molecules toward a condensate interface.

The model is deliberately minimal. Each protein is represented as a 25-bead coarse-grained polymer with two bead types arranged in a repeating block pattern, analogous to a simple block copolymer. Like beads attract one another through Lennard-Jones potentials, while unlike beads repel. Crucially, the two internal blocks of cohesive beads are stiffened by harmonic angular potentials, making them behave like rigid rods that stand in for β-prone, aggregation-prone motifs, while the intervening linkers remain floppy. This design separates cohesion from stiffness: a chain can be made more rigid without increasing its attraction strength, and the placement of its sticky motifs can be rearranged without changing the total amount of cohesive material. The simulations do not resolve residue-level chemistry, strand registry, or hydrogen-bond directionality, so the filaments they produce are coarse-grained analogs of amyloid rather than atomically resolved structures.

The simulation geometry mimics a driven cellular environment. Two semi-arrested condensate surfaces, built from 8,000 chains of the same molecular species, face each other across a dilute region. Up to 20,000 additional chains are then introduced at a prescribed deposition rate, each given an initial velocity directed toward the nearest interface—an initial kick that mimics the chemical-potential gradient dragging molecules toward the droplet surface in a living cell. Without this bias, inserted molecules would simply diffuse and aggregate in the dilute phase. Together, the deposition rate and the initial drift velocity define a minimal flux protocol for probing how non-equilibrium delivery shapes interfacial assembly.

The first major finding concerns rigidity. When chains with stiff β-prone segments were deposited onto the condensate interface, they formed anisotropic protrusions that extended away from the surface, elongated over time, bundled together, and eventually formed mesh-like structures capable of bridging the two opposing interfaces. Chains with the identical bead pattern but floppy backbones accumulated at the interface just as readily, yet relaxed into laterally spreading, disordered surface aggregates with no fibrillar character. Because the two simulations differed only in angular stiffness, the comparison identifies backbone rigidity as the variable that converts ordinary interfacial adsorption into directional fibrillar growth. When the researchers scrambled the placement of cohesive beads at fixed composition, the chains failed to form filaments altogether and instead promoted the growth of extended planar surfaces, underscoring that motif patterning matters as much as motif count.

Why does stiffness matter so much? The answer lies in the orientational field imposed by the interface itself. By measuring a nematic order parameter as a function of distance from the surface, the researchers found that condensate interfaces organize arriving chains into a layered structure before any large-scale assembly begins. Segments that directly contact the surface lie flat in the interfacial plane, approaching the theoretical planar limit of the order parameter within the first few bead diameters. Beyond this contact layer, the order parameter does not decay monotonically; instead, it alternates with a characteristic spacing of roughly eight bead diameters, with positive maxima indicating segments preferentially aligned along the interface normal. This spacing matches the separation between successive rod-like units along an extended chain, meaning that outer segments of surface-anchored chains project into the dilute region while their leading segments remain adsorbed. The result is a layered architecture—a planar contact layer followed by segments oriented outward—that is precisely the local arrangement a protruding fibril needs in order to elongate.

The second major axis of control is molecular flux. Material arriving at a condensate interface can be incorporated in two geometrically distinct ways: it can spread laterally, increasing surface coverage, or it can extend outward, increasing the height and volume of the growing assembly. Tracking the exposed area and convex-hull volume of the largest adsorbed cluster, the researchers showed that increasing the initial drift velocity dramatically accelerates surface coverage—reducing the time to reach a coverage shoulder from roughly 1,000 chain insertions at the slowest drift to about 300 at the fastest. But faster arrival came with a cost. When the researchers measured the elongation rate of individual filaments along their principal axis, they found that the longitudinal growth rate decreased systematically as the initial drift velocity increased, while the transverse thickening of the filaments depended only weakly on it. Faster molecules, in other words, cover the surface quickly but are less efficiently incorporated into the growing fibril tip.

The likely explanation is a competition between two fates for incoming chains. Chains that attach along the lateral surface of an existing protrusion mainly increase its radial extent, whereas chains captured near the filament tip contribute directly to axial elongation. A large initial drift velocity promotes rapid interfacial capture and surface coverage, starving the protrusion tip of material that could otherwise drive extension. The deposition rate and drift velocity act together to select the growth trajectory: frequent deposition favors protrusive growth when the initial drift is weak, whereas large drift velocities bias the system toward lateral spreading and suppress out-of-plane extension. Aging in this model, the authors conclude, is not a single pathway but a family of non-equilibrium trajectories selected by how material is delivered to, and captured by, the condensate interface.

The broader implications are considerable. Because sequence-encoded rigidity and molecular delivery are, in principle, independently tunable—through protein engineering on one hand and through expression level, exchange kinetics, transport, or chemical remodeling on the other—the framework suggests that aging trajectories of condensates could be redirected by modulating molecular delivery alone, without altering the protein sequence itself. The authors also propose mesoscale observables that bridge their simulations to experiments: convex-hull geometry to separate lateral coverage from anisotropic extension, a molecular loading ratio that reports how accumulated material distributes over the exposed aggregate area, and the gyration-tensor spectrum that identifies persistent symmetry breaking along the filament axis. These quantities do not require residue-level resolution and can be compared directly with microscopy-based morphology measurements.

The researchers are careful to note the limits of their abstraction. The model does not define a critical nucleus or measure nucleation rates and barriers, so they use the term interfacial fibril initiation rather than claiming to resolve a specific nucleation pathway. Each point in their morphology map corresponds to a single trajectory, making the map descriptive rather than a thermodynamic phase diagram, and the fibrils themselves are coarse-grained assemblies stabilized by cohesion and rigidity rather than residue-resolved amyloid. Still, the core message is clear and testable: the same protein can age along entirely different morphological routes simply because the rate and manner of molecular delivery change. If this separation between structural competence and transport control holds in cellular condensates, it opens a practical route to intervening in the earliest stages of amyloid disease—not by redesigning the proteins involved, but by changing how fast they arrive at the droplet surface where fibrils are born.

Subject of Research: Simulation study of how chain rigidity, motif patterning, and molecular flux control fibril growth at biomolecular condensate interfaces

Article Title: β motifs and molecular flux promote fibril growth at condensate interfaces

Article References: Biswas, S., & Potoyan, D. A. (2026). β motifs and molecular flux promote fibril growth at condensate interfaces. iScience, 29(11), Article 117855. https://doi.org/10.1016/j.isci.2026.117855

Image Credits: AI Generated

DOI: 10.1016/j.isci.2026.117855

Keywords: biomolecular condensates, amyloid fibrils, phase separation, molecular dynamics, protein aggregation, condensate aging, β-sheet motifs, molecular flux, hnRNPA1, FUS, neurodegenerative disease, coarse-grained simulation

Human cytomegalovirus, abbreviated HCMV, carries a double-stranded DNA genome of approximately 230 kilobase pairs, making it one of the larger viral genomes that replicates inside human cells. During lytic infection, when the virus actively produces new progeny, this genome is copied repeatedly and at high speed, a process that inevitably generates DNA lesions and replication-associated stress. Because HCMV does not encode a canonical set of DNA repair enzymes of its own, it must depend on the DNA damage response machinery of the host cell to keep its genome in a replicable state. How the virus directs host repair proteins specifically to its own DNA, rather than allowing them to disperse across the cellular genome, has remained a poorly understood question in virology.

The new work identifies MORC Family CW-type zinc finger 2, or MORC2, as a central player in answering that question. MORC2 is a host chromatin remodeler, an ATP-consuming enzyme that alters the packaging of DNA around histone proteins and thereby changes how accessible specific stretches of chromatin are to the proteins that act on them. The researchers found that HCMV infection induces the expression of MORC2 in infected cells, and that this induction is not incidental. When MORC2 was depleted, viral DNA replication became less efficient and the production of progeny virus dropped, indicating that the protein provides a tangible benefit to the viral life cycle.

A key observation of the study concerns the localization of MORC2 during infection. In uninfected cells, MORC2 is distributed in a pattern associated with its normal chromatin-related functions. Upon HCMV infection, however, the protein redistributes to viral replication compartments, specialized nuclear structures where viral genomes accumulate, are copied and are packaged into new virions. This relocalization places MORC2 physically at the sites where viral DNA is most vulnerable to damage and where the DNA damage response must be deployed if replication is to continue without catastrophic genome failure.

The mechanistic detail that emerges from the study is that MORC2 acts on the architecture of viral chromatin itself. Using its ATPase activity, the energy-consuming motor domain characteristic of this family of remodelers, MORC2 enhances the accessibility of viral chromatin. In practical terms, the viral genome, which is coated with nucleosomes and otherwise relatively compacted, becomes more open in the presence of active MORC2. This opening has a downstream consequence that lies at the heart of the paper: it facilitates the accumulation of gamma-H2AX, the phosphorylated form of histone variant H2AX that serves as the canonical beacon of DNA double-strand breaks and the organizing signal for the cellular damage response.

Gamma-H2AX is more than a passive marker. Its accumulation over damaged DNA creates a platform onto which repair factors are recruited, forming foci that coordinate sensing, signaling and repair of lesions. The researchers showed that MORC2-dependent chromatin opening at viral replication compartments facilitates the recruitment of these DNA repair factors to the viral genomes. In other words, the virus appears to use a host remodeling enzyme to prepare its own chromatin so that the damage response can be efficiently installed exactly where it is needed. Without MORC2, the signaling cascade on viral DNA is weakened, and the consequences for viral replication and progeny production follow directly.

Perhaps the most intriguing part of the study concerns how MORC2 is delivered to the viral replication compartments in the first place. The authors found that HCMV UL112-113, a viral locus whose products are known to participate in the early assembly of replication compartments, mediates a process of phase separation that facilitates MORC2 recruitment. Phase separation is a physical phenomenon in which proteins and nucleic acids condense into membrane-less compartments, a mechanism increasingly recognized as a general principle of cellular organization. In the context of HCMV infection, UL112-113-driven condensates appear to concentrate MORC2 within the viral replication compartments, ensuring that the remodeler acts preferentially on viral rather than host chromatin.

This recruitment mechanism ties together several threads of modern virology and cell biology. Large DNA viruses such as HCMV must build dedicated nuclear factories for genome synthesis, and phase-separated condensates have emerged as a structural principle of these factories. The new findings suggest that such condensates do more than concentrate viral replication proteins; they also serve as docking environments for host factors that the virus needs, in this case a chromatin remodeler that tunes the physical state of viral DNA. By coupling condensate formation to the recruitment of MORC2, the virus achieves a degree of selectivity that would otherwise be difficult to explain, given the enormous excess of host chromatin in the infected nucleus.

The broader significance of the work lies in the framework it provides for understanding how DNA viruses cope with replication stress. Rather than encoding its own repair machinery, HCMV appears to have evolved to co-opt host chromatin dynamics, converting a general host stress response into a virus-supportive program. The authors describe this as a mechanistic framework for how DNA viruses alleviate replication stress by hijacking host chromatin remodelers. Because MORC2 is required for efficient viral DNA replication and progeny production, the protein also emerges as a potential point of vulnerability for antiviral intervention, although the study itself is framed as basic mechanistic biology rather than therapeutic development.

For the field of herpesvirus biology, the study adds MORC2 to a growing list of host chromatin-associated factors whose services are enlisted by HCMV, and it connects the viral DNA damage response to the physical organization of replication compartments through phase separation. It also raises questions that future work will need to address, including which specific repair pathways are loaded onto viral genomes downstream of MORC2-mediated chromatin opening, and whether other DNA viruses deploy comparable strategies to remodel their chromatin during infection. What is already clear from the present findings is that the boundary between viral and host genome management is far more permeable than a simple list of viral genes might suggest, and that a 230-kilobase viral genome depends, in part, on the remodeling activities of the very cell it infects.

Subject of Research: How human cytomegalovirus recruits the host chromatin remodeler MORC2 to activate the DNA damage response on viral genomes during lytic infection.

Article Title: Human cytomegalovirus exploits host chromatin remodeler MORC2 to promote the DNA damage response on viral genomes

Article References: Jeong, J., Jeong, D., Lee, S., Park, J., Kim, H., & Ahn, K. (2026). Human cytomegalovirus exploits host chromatin remodeler MORC2 to promote the DNA damage response on viral genomes. PLOS Pathogens, 22(10), e1014693. https://doi.org/10.1371/journal.ppat.1014693

Image Credits: AI Generated

DOI: 10.1371/journal.ppat.1014693

Keywords: human cytomegalovirus, MORC2, chromatin remodeling, DNA damage response, viral replication compartments, gamma-H2AX, phase separation, UL112-113, herpesvirus, replication stress, PLOS Pathogens, viral chromatin

The story begins with a well-known stress signal. When plants receive more light than their photosynthetic apparatus can use, the excited state of chlorophyll can transfer energy to molecular oxygen, generating singlet oxygen, a highly reactive form of the molecule that damages proteins, lipids and nucleic acids. Singlet oxygen is not simply a toxic byproduct; in plant biology it also functions as a signal that reprograms gene expression and initiates protective responses. Previous work had established that one of the proteins responding to this signal is MBS1, which undergoes condensation when singlet oxygen accumulates. What remained unclear was exactly how the protein senses the oxidizing environment and what the resulting droplets actually do for the plant.

The new study characterized the precise conformational changes that drive the process, and the architecture it uncovered is elegantly modular. Singlet oxygen sensing occurs through a zinc-finger domain that is flanked on either side by two intrinsically disordered regions. Intrinsically disordered regions are stretches of protein that lack a fixed three-dimensional structure and are a hallmark of many proteins that form biomolecular condensates, the membraneless droplets that concentrate specific molecules through phase separation. The zinc-finger domain, meanwhile, provides the sensory trigger, allowing the protein to translate a chemical cue, the presence of singlet oxygen, into a physical transformation, the switch from a dispersed state into a condensed one.

Once MBS1 condenses, the consequences are visible at the level of whole organelles. The condensates that form are described as having low mobility, and they accumulate in the vicinity of chloroplasts, the green organelles where photosynthesis takes place. Rather than acting diffusely through biochemical signaling, these assemblies exert their effect through their biophysical properties: they scatter and absorb incoming light. In doing so, they reduce the photon flux reaching the photosynthetic machinery, effectively shielding it from the excess energy that would otherwise drive the production of even more reactive oxygen species. The condensates thus function as a self-assembled optical filter, deployed only when and where the danger of photodamage is highest.

This mechanism represents a conceptual shift in how biologists think about condensates in plants. Membraneless protein condensation has recently been shown to participate in signaling roles across many plant pathways, typically by concentrating substrates or sequestering specific molecules to modulate biochemical reactions. In those cases, the condensate is a regulatory compartment that changes the chemistry of its contents. The MBS1 work provides what is probably the first example in plants of protein condensates exerting a protective role through their physical properties instead, acting on light itself rather than on the concentration of reactants. The droplet is not a reaction vessel here; it is a shade cloth.

The photoprotective logic of the system is worth appreciating in detail. Photosynthesis depends on a delicate balance: light-harvesting complexes must capture enough energy to power carbon fixation, but any surplus excitation energy risks over-reducing the electron transport chain and generating reactive oxygen species. Plants already possess well-characterized mechanisms of non-photochemical quenching, in which excess excitation energy is dissipated as heat within the photosynthetic membranes themselves. The MBS1 condensates add an additional layer of protection that operates outside the thylakoid membrane, intercepting light before it even reaches the photosystems. Because the condensates form in response to singlet oxygen, the very molecule produced by light stress, the system operates as a feedback loop: stress generates the signal, the signal assembles the shield, and the shield reduces the stress.

Perhaps the most consequential result is the demonstration that the mechanism can be engineered for crop improvement. When the researchers overexpressed MBS1, the resulting rice plants showed enhanced protection, and this held up not only under controlled conditions but also in field trials. Field validation is a critical hurdle for any photoprotection strategy, because laboratory light regimes rarely capture the fluctuating intensity, spectral quality and thermal stress that crops experience in an open field. The observation that extra MBS1 confers measurable protection in real agronomic conditions suggests that the condensate-based sunscreen is robust enough to matter for agriculture, particularly as heat waves and high-light episodes become more frequent and more severe.

The implications extend beyond rice. Rice is a staple crop feeding billions of people, and yield losses from abiotic stress, including excess light combined with heat and drought, are a persistent concern for breeders. A single gene whose overexpression enhances phototolerance offers a tractable target for both conventional breeding and biotechnology. Because the protective agent is a protein that the plant already possesses, the engineering involved is a matter of dosage rather than the introduction of foreign functions, which may simplify regulatory and public acceptance pathways in some jurisdictions. The study also suggests that homologous pathways in other crops could be examined for similar condensate-mediated photoprotection.

From a broader scientific perspective, the work connects several active research threads. Biomolecular condensates have become one of the most dynamic areas of cell biology over the past decade, with roles proposed in transcription, stress granule formation, and signal transduction across eukaryotes. Plant science has contributed evidence that condensates participate in hormone signaling, immune responses and developmental transitions. The MBS1 system adds a new functional category to this growing list and demonstrates that the material properties of condensates, their ability to scatter and absorb light, can themselves be the selective advantage that the condensation evolved to provide. It also highlights the versatility of intrinsically disordered regions, which in this case are not merely scaffolds for droplet formation but are coupled to a sensory zinc-finger domain that reads the redox state of the chloroplast environment.

Questions naturally remain. The precise optical properties of the condensates, the molecular composition of the droplets beyond MBS1 itself, and the dynamics of their assembly and dissolution as light conditions fluctuate are all subjects for further investigation. Understanding how the zinc-finger domain detects singlet oxygen at the atomic level, and how the disordered regions tune the material state of the condensates, could allow researchers to tune the response deliberately. But the central message of the study is already clear and, in its way, quite beautiful: under the harshest light of the day, a plant cell can condense a protein into microscopic sunshades around its chloroplasts, and endowing crops with more of that protein helps them stand up to the sun. What began as an observation about a singlet-oxygen-responsive protein has matured into a validated photoprotective mechanism with demonstrated value in the field, offering both a new chapter in the biology of membraneless organelles and a practical tool for the crops of a warming, brighter world.

Subject of Research: Singlet oxygen-induced MBS1 protein condensates that photoprotect chloroplasts and enhance rice stress tolerance

Article Title: Sunscreen condensates

Article References: Tena, G. (2026). Sunscreen condensates. Nature Plants. https://doi.org/10.1038/s41477-026-02451-0

Image Credits: AI Generated

DOI: 10.1038/s41477-026-02451-0

Keywords: MBS1, singlet oxygen, biomolecular condensates, chloroplasts, photoprotection, light stress, intrinsically disordered regions, zinc-finger domain, phase separation, rice, photosynthesis, crop improvement

The system centers on an RNA nanostar, a single RNA strand that folds cotranscriptionally into four arms separated by single uracils, each arm terminating in a self-complementary kissing-loop motif. These kissing loops allow nanostars to bind one another and, at sufficient concentration, to condense into liquid droplets through liquid-liquid phase separation. Unlike most nucleic acid condensates, which assemble through nonspecific electrostatic interactions between polycations and polyanions, these droplets are held together by sequence-specific base pairing, which means the droplet’s material properties are written directly into its sequence. Two arms carry 25-base-pair duplex stems, a third carries a malachite green aptamer for fluorescence imaging, and the fourth carries a biotin aptamer for recruiting molecular targets. Crucially, the DNA template that encodes the nanostar remains in the reaction mixture as the droplets form.

The first question the team addressed was whether the droplets actually trap their own genes. By labeling the DNA template with fluorescein-labeled dUTP and imaging with confocal microscopy, the researchers found that the DNA is localized within the RNA droplets rather than dispersed in solution. The DNA is not distributed evenly; instead it forms hotspots one to three micrometers across, likely arising from sequence-specific RNA-RNA interactions combined with electrostatic repulsion between DNA and RNA. A plausible mechanism is cotranscriptional capture: nascent nanostar RNA folds and engages in multivalent interactions while still tethered to the DNA through the RNA polymerase, dragging the template into the condensate as it assembles. This establishes a physical genotype-phenotype link, the first prerequisite for an evolvable system.

With that link in place, the researchers asked whether mutations in the DNA would change the droplet phenotype. Exploiting the self-complementarity of the template, they used PCR to generate a pool of mutated genes, dubbed Mut DNA. The result was striking: transcription of Mut DNA consistently produced vacuolated droplets, hollow spheres containing stable internal cavities, whereas the unmutated wild-type template produced only homogeneous spherical droplets. Vacuoles appeared in 74 percent of Mut droplets with radii above 15 micrometers and in 94 percent of those above 25 micrometers, while no wild-type droplet ever showed a vacuole. Time-lapse imaging revealed that these cavities nucleate after roughly two hours of transcription, become clearly visible by six hours, and then persist and grow for at least 50 hours, remaining stable for days. This longevity distinguishes them from the short-lived vacuoles previously reported in DNA droplets, which lasted less than an hour.

Control experiments ruled out the obvious alternative explanations. Adding RNase inhibitors had no effect on vacuole formation, and wild-type droplets remained intact and vacuole-free even after 13 days at 37 degrees Celsius, indicating that enzymatic degradation was not responsible. Environmental conditions such as temperature and pH were held constant throughout, so the vacuole phenotype could be attributed to the mutations themselves. Gel electrophoresis of the PCR product revealed two additional bands beyond the main wild-type band: longer fragments, probably generated by self-priming of the template, and shorter fragments from spurious mispriming. When the team gel-purified each band and transcribed them separately or in combination, only preparations containing the longer nonspecific products produced vacuolated droplets on their own, while the shorter products caused vacuolation only when mixed with the main band. The nonspecific PCR products, mostly deletion and duplication mutations, were therefore the genetic cause of the hollow phenotype.

To show that this was not an artifact of one particular mutagenesis route, the researchers turned to substitution mutagenesis, the workhorse of directed-evolution experiments. Using dNTP analogs during PCR, they introduced point mutations into a second nanostar template while sparing the promoter region, controlling the mutation rate through the number of analog cycles. Four distinct phenotypes emerged depending on mutational load: normal droplets, vacuolated droplets, a percolating RNA network, and simple aggregates. Remarkably, a mutation rate of only about three percent, corresponding to roughly seven altered bases per nanostar template, was enough to trigger vacuole formation. An orthogonal error-prone PCR protocol using manganese ions to reduce the fidelity of Taq polymerase produced the same vacuolated phenotype, confirming that substitution mutations are a general route to increased phenotypic complexity in these droplets.

To understand the mechanism, the team sequenced the mutated DNA with long-read nanopore sequencing and found that 94.7 percent of reads still matched the wild type, consistent with the low mutation threshold. The remaining 5.3 percent encoded various nanostar-like structures retaining at least one kissing loop, the most common being a four-armed nanostar with three functional kissing loops. The researchers reverse-engineered this dominant mutant as a defined nanostar, termed Mut RNA, and mapped the thermodynamic phase diagram of wild-type and mutant nanostars by measuring RNA concentrations inside and outside the condensates. Fitting the data with an effective free energy density revealed that phase separation is driven by adhesive interactions among the nanostars, that mutant-mutant interactions are less adhesive than wild-type-wild-type interactions, and that the mutant’s slightly larger molecular volume matches its slightly longer arm.

The phase diagram enabled a quantitative explanation of vacuole formation. As transcription proceeds, the ratio of mutant to wild-type nanostars is fixed by the mutant DNA fraction, but droplet growth outpaces internal diffusion, generating concentration gradients within the droplet. When these gradients push the local composition across the spinodal line, a local instability fires inside the droplet, creating a new internal interface, in other words, a vacuole. A kinetic model built on the measured phase diagram and transcription rates predicted that vacuoles can only form in droplets with radii above roughly 21.5 micrometers, because in smaller droplets diffusion erases the gradients, and only when the mutant fraction exceeds about two percent, because the mutant’s higher internal diffusivity favors crossing the spinodal. Both predictions matched the experiments. Imaging also showed no enrichment of mutant RNA at the water-condensate interface, ruling out a surfactant stabilization mechanism; the vacuoles’ long lifetime instead reflects the high viscosity of the RNA-rich phase, which makes vacuole coalescence vanishingly rare.

The most striking finding is that the vacuoles are not merely structural. Vacuolated droplets exhibit micrometer-scale movement over more than 50 hours, characterized by irregular, burst-like displacements. Tracking experiments showed significantly enhanced motility compared with wild-type droplets, and because moving droplets collide more often, the mutants fused more frequently and grew larger. The mechanism is internal mass redistribution: as vacuoles nucleate and grow, they displace dense RNA, shifting the droplet’s center of mass. Measuring the angle between vacuole displacement and droplet displacement confirmed this, with the most frequent angles falling between 174 and 180 degrees, meaning the vacuole and droplet center move in opposite directions. Unlike previously reported moving DNA droplets, the vacuoles remain stable throughout the trajectory and movement can occur repeatedly, without a persistent polarity or propulsion axis. Beyond motility, the vacuoles act as functional subcompartments: the dense RNA matrix excludes 50-nanometer lipid vesicles, but 50-kilodalton dextran, roughly 10 nanometers across, diffuses through the matrix and accumulates selectively inside the vacuoles, while the encoded biotin aptamer recruits biotinylated vesicles to the droplet surface as a shell.

Together, the results establish RNA droplets as self-contained, evolvable systems that satisfy the prerequisites of Darwinian evolution: retention of genetic material, mutation-driven phenotypic variability, and the emergence of selectable functional traits. The authors suggest that selection could, for example, favor increasingly hollow droplets, evolving toward a vesicle-like RNA condensate, and that future work could integrate ribozymes and aptamers to encode dynamic behavior as a starting point for open-ended evolution. Because sequence programmability can be extended with aptamers for specific molecular recruitment or with the catalytic abilities of ribozymes, the platform points toward evolvable materials with applications in biomedicine and biotechnology, from self-propelled microswimmers to drug delivery systems. It may also inform one of science’s oldest questions, offering a concrete experimental model for how genetic information, compartmentalization and selectable phenotypes could have first become coupled in an RNA world, when nonliving molecular assemblies took their first steps toward life.

Subject of Research: Genetic encoding, mutagenesis and evolvability of RNA nanostar droplets as protocell models

Article Title: Genetic encoding and mutagenesis of RNA droplet phenotypes

Article References: Verstraeten, W., Tran, M. P., Taskina, A., Jaiswal, P., Haugerud, I. S., Helbig, C., Hamberger, M., Green, E. W., Platten, M., Weber, C. A., & Göpfrich, K. (2026). Genetic encoding and mutagenesis of RNA droplet phenotypes. Nature Chemical Engineering. https://doi.org/10.1038/s44286-026-00454-4

Image Credits: AI Generated

DOI: 10.1038/s44286-026-00454-4

Keywords: RNA droplets, liquid-liquid phase separation, synthetic cells, protocells, mutagenesis, vacuoles, kissing-loop interactions, DNA template, phase separation, origins of life, cotranscriptional folding, directed evolution

The protein at the center of the study is GTBP-1, the worm equivalent of human G3BP1, a molecule long recognized as a master organizer of stress granules. Stress granules are dynamic, membrane-less assemblies of stalled messenger RNAs and proteins that form rapidly when cells encounter harsh conditions such as heat, oxidative damage, or nutrient deprivation. By temporarily sequestering mRNAs, these condensates pause protein production and shield RNA transcripts from degradation, buying the cell time to recover. In mammalian cells, G3BP1 acts as a molecular switch that triggers the phase separation driving stress granule assembly, making its worm counterpart an obvious candidate for investigating how germ cells weather thermal stress.

To probe GTBP-1’s role, the team used CRISPR/Cas9 to generate knockout worms lacking the gene entirely. The results were strikingly temperature-dependent. At cool temperatures of 15 and 20 degrees Celsius, gtbp-1 mutants actually produced more offspring than normal worms, suggesting the protein normally restrains reproduction under benign conditions. But when animals were raised at 25 degrees Celsius, the mutants became severely infertile. Microscopy showed that the germline tissue itself remained largely intact in the heat-stressed mutants, yet embryos were rarely seen, indicating that the fertility collapse stems from a failure in embryo production rather than a wholesale loss of reproductive tissue. GTBP-1, it appears, is dispensable or even slightly inhibitory when life is easy, but essential when the heat is on.

Fluorescent tagging revealed the protein’s dramatic behavioral shift. Under standard laboratory conditions, GFP-labeled GTBP-1 drifted diffusely through the cytoplasm of epidermal cells, germ cells, and early embryos. When worms were chronically cultured at 25 degrees Celsius, punctate GTBP-1 granules appeared in the germline of a subset of animals, though not in skin cells. Acute heat shock at 37 degrees Celsius for just 30 minutes produced even more pronounced granules across multiple tissues, with GTBP-1 condensing into structures at the perinuclear region surrounding germ cell nuclei, within the central rachis of the gonad, and in the cytoplasm of oocytes. The message was clear: heat stress rapidly reorganizes this protein from a dispersed state into concentrated assemblies precisely where reproductive RNA management happens.

The researchers then dissected which parts of the protein matter. GTBP-1 carries several conserved domains: an NTF2 domain, an intrinsically disordered region, an RNA recognition motif, and an arginine/glycine-rich region. Deleting the NTF2 domain nearly abolished GTBP-1’s recruitment into heat-induced granules, confirming that this module, already known to drive G3BP1-mediated condensation in mammals, is the engine of granule assembly. Deleting the disordered region or the RGG domain told a different story: granules still formed during heat stress but lingered far longer during recovery, indicating these domains govern the fluidity and reversibility of the condensates. Notably, all four domain-deletion variants showed reduced fertility at 25 degrees Celsius, and the severity of the reproductive defects did not simply track with granule defects, hinting that GTBP-1’s contributions to reproduction extend beyond granule formation, possibly through RNA-related functions of its binding domains.

Where exactly do these granules sit within the crowded landscape of germ cell structures? The C. elegans germline hosts an impressive array of perinuclear condensates, including P granules, Z granules, Mutator foci, SIMR foci, D granules, E granules, and P-bodies, each with distinct molecular markers and functions in small RNA metabolism and gene silencing. By crossing their GFP::GTBP-1 strain with strains carrying fluorescent markers for all seven compartments, the team quantified overlap after heat shock. The verdict was unambiguous: GTBP-1 showed its strongest correlation with the P-body marker CGH-1, with moderate associations to several other compartments and a notably weaker link to Z granules. The same GTBP-1 and CGH-1 pairing appeared in both mitotic and meiotic regions of the germline and persisted in early embryos through the two-cell, four-cell, and multicellular stages.

P-bodies are condensates dedicated to mRNA storage and decay, and their intimate relationship with stress granules has been documented in yeast and mammalian cells, where the two structures exchange messenger ribonucleoprotein components under stress. The worm study adds a germline dimension to this picture. When the researchers depleted core P-body components such as CGH-1, EDC-3, or IFET-1 by RNA interference, heat-induced GTBP-1 enrichment dropped significantly, both in the perinuclear region and in the rachis, while total GTBP-1 protein levels remained unchanged. In contrast, disrupting P, Z, Mutator, or E granule components did not prevent GTBP-1 from forming puncta. P-body organization, in other words, is specifically required for efficient GTBP-1 granule assembly during heat stress, positioning these mRNA-decay condensates as scaffolds or partners for the stress response in germ cells.

A candidate screen of 35 genes encoding stress granule proteins and predicted GTBP-1 interactors added further regulators to the network. Loss of PQN-59, a protein related to human UBAP2L, reduced both GTBP-1 granule enrichment and granule number, whereas depletion of the stress granule protein TIAR-1 had little effect. Two other hits stood out: LAF-1, a DEAD-box RNA helicase best known as a P granule component that drives phase separation, and SMO-1, the worm’s sole SUMO protein, implicating SUMOylation, a stress-elevated protein modification, in granule regulation. None of these depletions changed total GTBP-1 abundance, and none rescued the fertility of gtbp-1 mutants at 25 degrees Celsius, showing that granule disruption alone cannot restore reproduction.

The most surprising discovery came from a forward genetic screen of roughly 20,000 mutagenized genomes, hunting for mutations that restore fertility to heat-stressed gtbp-1 mutants. Only one suppressor emerged repeatedly: loss-of-function mutations in rsks-1, the worm homolog of ribosomal S6 kinase, a key effector of the mTOR signaling pathway that governs translation, growth, and aging. Knocking out rsks-1 by several independent means consistently rescued the brood size of gtbp-1 mutants at 25 degrees Celsius, while depleting a panel of well-known longevity genes did not, arguing that the effect is specific rather than a general slowdown of aging pathways. Heat-shock survival assays added nuance: rsks-1 mutants alone were more sensitive to lethal heat, but combining rsks-1 loss with gtbp-1 loss restored wild-type survival, suggesting the two proteins counterbalance each other in stress responses.

RSKS-1 also turned out to be a heat-responsive granule protein in its own right. Normally distributed throughout the cytoplasm and nucleus, it relocalized after heat shock into perinuclear granule-like structures in the germline and oocytes, and these structures overlapped substantially with CGH-1-positive P-bodies, yielding a mean Pearson’s correlation coefficient of about 0.67. Loss of RSKS-1 delayed the appearance of GTBP-1 granules and reduced their number during heat stress without changing how strongly GTBP-1 concentrated within individual granules, indicating that the kinase controls the kinetics and abundance of granule formation rather than granule composition. Together, the findings sketch a working model in which heat stress recruits GTBP-1, along with PQN-59, TIAR-1, and RSKS-1, into perinuclear P-body-associated condensates, linking mTOR-dependent translational control to the RNA granule remodeling that keeps fertility intact across a changing thermal world. As heat waves intensify and reproductive health under thermal stress becomes an ever more pressing question from agriculture to human fertility, this humble worm offers a molecular map of how germ cells fight back.

Subject of Research: Heat stress-induced GTBP-1 stress granule assembly and its association with P-bodies in the C. elegans germline

Article Title: Heat stress promotes GTBP-1 association with perinuclear P-bodies in the C. elegans germline

Article References: Zang, D., Jing, Y., Huang, X., Kuang, Y., Cheng, J., Wang, W., Xu, D., Zhu, C., Chen, D., Zhao, Z., Feng, X., & Guang, S. (2026). Heat stress promotes GTBP-1 association with perinuclear P-bodies in the C. elegans germline. PLOS Genetics, 22(10), e1012336. https://doi.org/10.1371/journal.pgen.1012336

Image Credits: AI Generated

DOI: 10.1371/journal.pgen.1012336

Keywords: stress granules, GTBP-1, G3BP1, C. elegans, germline, heat stress, P-bodies, fertility, mTOR signaling, RSKS-1, phase separation, RNA granules

The study, published in the Proceedings of the National Academy of Sciences, was led by ecologist Paul Berghuis, who is affiliated with Utrecht University and the Royal Netherlands Institute for Sea Research, known as NIOZ. Berghuis specializes in spatial ecology, a field concerned with the patterns that emerge from the interplay between organisms and their environment. His subject was the relationship between marram grass and sand, a pairing long known to be central to dune formation. Marram grass traps windblown sand around its stems, and over years the trapped sand accumulates into the embryonic dunes that eventually grow into the protective barriers shielding much of the Dutch coastline. What Berghuis set out to determine was not how a single plant builds a single dune, but how thousands of plants and dozens of dunes interlock into a coherent landscape.

To answer that question, Berghuis turned to a source of information that spans decades: aerial photographs. By analyzing these images through time, he searched for fixed patterns in the way young dune landscapes arrange themselves. The approach deliberately shifted the scale of inquiry. As Berghuis explains, quite a lot is already known about individual plants and the processes acting on them, but the deeper question concerns how the complex system of sand and vegetation fits together as a whole. That question dictated the scale at which the dunes were studied. Rather than treating the landscape as a collection of individually operating grasses and dunes, he examined it as a system that organizes itself at the landscape level. Seen that way, he found, the dune landscape displays characteristics of growth and resilience that cannot be predicted from the behavior of individual dunes or grasses alone.

The first surprise was what the patterns were not. In previously studied ecosystems that self-organize, such as mussel beds or the patchy vegetation of savannas, a regular arrangement typically emerges: spots of roughly the same size, spaced at roughly the same distances, repeating across the landscape like a biological wallpaper. Dune landscapes break that rule. Berghuis discovered that there is no fixed size to the dune bodies at all. The reason lies in the restless nature of sand. Wind moves grains again and again before they finally settle somewhere, and the places where they settle are not chosen at random. Where marram grass plants grow closely together, the sand is retained most effectively. At these high densities of vegetation, a dune continues to grow, and it often does so at the expense of its neighbors. Small dunes are left behind or disappear entirely, while larger dunes merge together into ever bigger bodies.

That behavior, in which large units grow while small ones shrink and vanish, is the signature of a well-known physical process called phase separation. Co-author Koen Siteur and other colleagues had previously argued that the spatial organization of certain ecosystems resembles this physics, and the dune findings confirm the analogy with striking precision. Phase separation is familiar from the kitchen: when oil and vinegar are shaken together to make salad dressing, the oil first disperses into countless small droplets suspended in the vinegar. Left to stand, however, the droplets coalesce. Large droplets grow at the expense of small ones, because the physics of the interface between oil and vinegar favors consolidation. The same logic, the researchers found, governs sand and marram grass. Densely vegetated dunes capture sand more efficiently, drawing it away from sparsely vegetated neighbors, so the landscape coarsens over time much as the oil in a dressing does.

Crucially, the resemblance is not merely visual. Siteur’s theory, developed in earlier work, describes how phase-separating systems can be recognized by a very specific fingerprint in their statistics, and Berghuis reports that the dunes carry exactly that fingerprint. The distribution of dune sizes, the way in which dunes merge with one another, and even the rate at which the merging slows down over time all match what the theory of phase separation predicts. This is a significant scientific advance, because it moves the field from description to explanation. As Berghuis puts it, the researchers now know not only how dunes behave but also why they do so. A landscape that once seemed to be the idiosyncratic product of local wind and plant conditions is revealed to obey a general physical law, placing coastal dunes in the same theoretical family as droplets, alloys, and other systems that separate into distinct phases.

The practical consequences of that insight are considerable, because the theory does more than describe patterns; it makes predictions about how such systems respond to disturbance. According to the theory, damage to the spatial pattern does not heal itself once it exceeds a critical threshold. In a dune landscape, this could happen when marram grass is disturbed by trampling, or when wind scours a small pit in the sand. Intuition might suggest that such wounds would gradually fill in and recover, as many ecosystems do. The theory says otherwise. The disturbances are not repaired; instead, the sand that would be needed to heal them migrates away to the more densely vegetated dunes elsewhere in the landscape, reinforcing the winners and abandoning the losers. Local damage, in other words, can become permanent even while the system as a whole appears healthy.

Berghuis’s measurements show exactly such a threshold value in the amount of marram grass present. Below a certain vegetation density, the self-repair mechanisms of the dune system fail, and degradation becomes self-perpetuating. At the same time, the theory predicts that the system as a whole remains resilient in a particular sense: the sand is not lost from the landscape but merely redistributed, flowing from damaged or sparse areas toward the densely vegetated dunes that continue to grow. This dual character, locally fragile but globally stable, is precisely the kind of behavior that phase-separation theory is built to capture, and it fundamentally changes how coastal managers should interpret the landscapes they oversee. A dune area can look robust in aggregate while individual dunes, once pushed past their local tipping point, never recover.

For the philosophy of building with nature, these findings arrive at an opportune moment. As sea levels rise, the Netherlands and other coastal nations are betting increasingly on natural dune growth as a flexible, self-reinforcing line of defense, one that can keep pace with changing conditions in ways that fixed structures cannot. But that bet depends on knowing where the system’s limits lie. The new research supplies a quantitative answer: local damage can be permanent once vegetation density falls below a critical threshold, even if the dune area as a whole remains healthy, so management must attend to the fine-grained pattern of grass cover and sand, not merely to the total volume of the dune field. For anyone who wants to build with nature rather than against it, Berghuis argues, insights of this kind are crucial. The dunes, it turns out, have been organizing themselves all along according to rules written in physics, and learning to read those rules may determine how well the coast weathers the century ahead.

Subject of Research: Spatial self-organization and phase-separation dynamics in coastal dune formation

Article Title: Local tipping points in dune landscapes: how does a dune system organize itself?

Article References: Local tipping points in dune landscapes: how does a dune system organize itself?. (n.d.). Original publication

Image Credits: AI Generated

DOI: Not provided

Keywords: coastal dunes, marram grass, self-organization, phase separation, spatial ecology, tipping points, coastal management, building with nature, Utrecht University, NIOZ, PNAS, sea level rise

Writing in the journal Advanced Composites and Hybrid Materials, Insun Woo, Chaelin Park, and their colleagues at the Korea University of Technology and Education and the Korea Research Institute of Chemical Technology describe a one-step spray-coating strategy that simultaneously forms fibers, builds hierarchical micro- and nanostructures, and drives spontaneous phase separation within the coating. The key insight is that rapid solvent evaporation during spraying can do the work that high-voltage electric fields normally perform. As the atomized droplets of a blended polymer solution hit the substrate and the solvent flashes away, the two polymers in the mixture—silicone-based polydimethylsiloxane, or PDMS, and the ferroelectric copolymer poly(vinylidene fluoride-co-trifluoroethylene), abbreviated P(VDF-TrFE)—demix on their own according to their surface energies. The result is a self-stratified hybrid fibrous composite, assembled in a single pass without any high-voltage equipment at all.

The stratification is not a random accident but a compositionally graded architecture with a deliberate logic to it. PDMS, with its low surface energy and famously hydrophobic, electron-donating character, migrates to the exterior of the fibrous network, forming an enriched sheath at the outer surface. P(VDF-TrFE), a fluorinated copolymer prized for its high dielectric constant and strong charge-trapping ability, concentrates in the interior of the fibers. This spontaneous sorting matters because the two polymers play complementary roles in a triboelectric device. The outer PDMS-rich layer is the material that actually touches and separates from the counterface during operation, so its strong tribopositive character boosts charge transfer at the interface. The inner P(VDF-TrFE)-rich core, meanwhile, acts as a high-capacity reservoir that stabilizes and retains the generated charge, preventing the losses that normally erode output over time.

One of the most technically significant consequences of this self-stratification is its effect on the crystalline structure of the fluoropolymer. P(VDF-TrFE) can crystallize in several polymorphic phases, but the one that matters for electromechanical and dielectric performance is the β-phase, in which the fluorine and hydrogen atoms on the polymer backbone are arranged to give each chain a permanent dipole moment. The researchers found that the fibrous, PDMS-templated environment promotes β-phase crystallization within the P(VDF-TrFE)-rich interior, effectively polarizing the core of the material without the need for corona poling or other post-treatments in the way many conventional composites require. Combined with the enlarged effective contact area provided by the hierarchical fiber morphology, the graded structure delivers synergistic gains: more charge is generated at the surface, more charge is retained in the bulk, and more of that charge is converted into useful electrical output.

The numbers reported for the optimized device are impressive for a spray-coated architecture. The triboelectric nanogenerator produces an open-circuit voltage of 290 volts and a short-circuit current of 7.5 microamperes, with a maximum power density of 1.23 watts per square meter. For context, these output figures place the spray-coated composite in the same performance territory as fiber-based TENGs fabricated by electrospinning, but from a process that is inherently compatible with roll-to-roll coating, large-area deposition, and low-cost manufacturing. The fibrous network’s large surface area and mechanical flexibility—qualities that have made electrospun mats attractive in the first place—are preserved, while the fabrication barrier that has limited scalability is removed.

Durability is where many triboelectric devices stumble, since repeated contact and separation cycles can wear surfaces, degrade interfaces, and bleed away stored charge. The Korean team subjected their devices to extended endurance testing and found that the output remained stable over 30,000 mechanical cycles. That robustness is attributed in large part to the PDMS-enriched sheath, which is both mechanically resilient and chemically inert, shielding the underlying ferroelectric core while maintaining a consistent contact surface. Stable long-term output is a prerequisite for any practical deployment, whether the device is embedded in a wearable, laminated onto a floor, or integrated into an interactive surface that will be touched thousands of times a day.

What elevates the work from a materials demonstration to a systems-level advance is the pair of working applications the researchers built with their coatings. In one, a TENG-based sensor array was used for handwritten letter recognition: as a stylus or finger traces characters across the spray-coated surface, the pattern of electrical pulses generated by contact and separation encodes the writing dynamics, allowing the letters to be identified from the signal alone. In the other, the same class of device was integrated into a smart door lock, where the mechanical act of touching or interacting with the lock generates the electrical signal that operates it. Both demonstrations point toward self-powered sensing systems—interfaces that harvest the energy of the interaction they are measuring, eliminating batteries and wiring for low-power applications.

The broader implications reach into several fast-growing fields. Human–machine interfaces, from touch-sensitive prosthetics to gesture-recognition surfaces, need sensors that are flexible, durable, and cheap to produce at scale; a spray-coatable triboelectric layer checks all three boxes. Large-area energy harvesting—converting the mechanical energy of wind, rain, foot traffic, or vibration into electricity—has been limited by the cost and throughput of nanofabrication, and a one-step spray process could change the economics of covering square meters rather than square centimeters. And because the self-stratification mechanism is driven by fundamental thermodynamics—surface energy differences and solvent evaporation rates—the same principle could plausibly be extended to other polymer pairs, opening a design space of graded fibrous composites tailored for specific electronic functions.

The study, published open access on 5 September 2026 and citable under DOI 10.1007/s42114-026-02068-z, was supported by the National Research Foundation of Korea, the BK-21 FOUR program, the Korea Research Institute of Chemical Technology Core Research Program, and the Korea Planning and Evaluation Institute of Industrial Technology. The authors, including corresponding researchers Jin Woo Bae, Ju Hyeon Kim, and Eun-Ho Sohn, declare no competing interests. As with any early-stage materials research, questions of long-term environmental stability, manufacturability at true industrial scale, and integration with power-management electronics remain to be fully resolved. But the central achievement stands on its own: a fibrous, hierarchically structured, compositionally graded triboelectric material made in one step, with a spray gun, no high voltage, and performance that rivals the laboratory gold standard. Sometimes the most elegant solution to a fabrication bottleneck is to let physics do the assembly.

Subject of Research: One-step spray-coated self-stratified PDMS/P(VDF-TrFE) hybrid fibrous composites for triboelectric nanogenerators

Article Title: One‑step spray‑coated self-stratified PDMS/P(VDF‑TrFE) hybrid fibrous composite-based Triboelectric Nanogenerators

Article References: Woo, I., Park, C., Jo, B. E., Yoon, J.-M., Kim, D. H., Bae, J. W., Kim, J. H., & Sohn, E.-H. (2026). One‑step spray‑coated self-stratified PDMS/P(VDF‑TrFE) hybrid fibrous composite-based Triboelectric Nanogenerators. Advanced Composites and Hybrid Materials. https://doi.org/10.1007/s42114-026-02068-z

Image Credits: AI Generated

DOI: 10.1007/s42114-026-02068-z

Keywords: triboelectric nanogenerator, spray coating, self-stratification, PDMS, P(VDF-TrFE), fibrous composites, phase separation, energy harvesting, self-powered sensors, human-machine interfaces, beta-phase crystallization, hybrid materials

Phase separation is the physical phenomenon by which a well-mixed solution splits into distinct phases, the way oil separates from vinegar in a shaken bottle of salad dressing. In cells, proteins containing intrinsically disordered, low-complexity domains can drive the formation of membraneless compartments called condensates, which concentrate specific molecules without any enclosing lipid membrane. Nucleoli, stress granules and nuclear speckles all form this way. The key property of healthy condensates is dynamism: molecules diffuse in and out, and the entire assembly can dissolve within seconds or minutes once conditions change. This liquid-like behavior depends on weak, multivalent interactions among the low-complexity domains, which constantly break and reform.

The trouble begins when those weak interactions stop being weak and transient. The review describes how, in ALS, condensates formed by RNA-binding proteins such as FUS and TDP-43 progressively lose their reversibility, maturing from liquid droplets into gel-like states and eventually into solid fibrillar aggregates that are hallmarks of the diseased motor neuron. This liquid-to-solid transition, sometimes called pathological hardening, is driven by the same low-complexity domains that make condensates form in the first place. Given time, the transient beta-sheet-like contacts within these domains can lock into stable structures, converting a dynamic organelle into an irreversible inclusion that the cell cannot dismantle.

What makes the new review distinctive is its emphasis on the layers of cellular regulation that normally prevent this maturation. The authors assemble evidence that molecular chaperones, best known for helping newly made proteins fold, also patrol condensates. Heat shock protein 70 family members, for example, can bind exposed hydrophobic stretches within condensates, remodel their internal organization and keep the assemblies fluid. Chaperone activity thereby extends the window in which a condensate remains reversible, buying the cell time to dissolve it before aggregation becomes permanent. When chaperone capacity is overwhelmed or declines, as it does with age and stress, that window narrows.

Nuclear import receptors form a second, perhaps more surprising, line of defense. Karyopherin-beta2, the receptor that ferries FUS into the nucleus, does more than transport. It binds directly to the proline-tyrosine nuclear localization signal within FUS and, in doing so, physically shields the low-complexity domain from engaging in the multivalent contacts that drive phase separation and fibrillization. In effect, the import receptor acts as a portable anti-aggregation chaperone, keeping FUS soluble during its journeys through the cytoplasm. The review highlights how this mechanism illustrates a broader principle: compact folded domains can modulate the behavior of disordered regions they are physically linked to or bound against.

The proteostasis network supplies a third layer of regulation. Enzymatic components such as protein disulfide isomerase and peptidyl-prolyl cis-trans isomerase A can alter the conformational state of proteins inside or near condensates, while ubiquilin-like protein 2, an ALS-linked protein, helps shuttle ubiquitinated cargo between condensates and the protein degradation machinery. Optineurin, another ALS-associated factor, participates in autophagic clearance of aggregates. Together these systems form a quality-control pipeline that continuously remodels and removes material from condensates, limiting the residence time of any given molecule and thereby reducing the probability that transient contacts will ripen into stable aggregates.

The review then turns to one of the most devastating genetic insults in ALS: the hexanucleotide repeat expansion in the C9ORF72 gene, the most common known cause of familial disease. This expansion produces arginine-rich dipeptide repeat proteins, and these short, highly basic peptides are potent modifiers of phase behavior. They can seed the condensation of RNA-binding proteins and, critically, impair nuclear import pathways, including the transport receptors that keep FUS in check. The result is a double hit: more condensation is promoted at the same time as the systems that would normally reverse it are disabled. The authors present this as a mechanistic explanation for why C9ORF72 pathology so closely resembles the FUS and TDP-43 proteinopathies seen across the ALS spectrum.

Perhaps the most forward-looking section of the review concerns zinc finger domains. Recent structural and biophysical studies suggest that these small, compact, folded modules can recognize specific polymer states of low-complexity domains and constrain their growth. Rather than dissolving condensates outright, zinc finger domains appear to cap or crosslink the polymers in ways that limit further elongation and material transition. This supports what the authors describe as a model in which structured domains act as modulators of higher-order assemblies, reading the physical state of a condensate and restraining its maturation. If confirmed across multiple ALS-associated proteins, this recognition mechanism could represent an entirely new regulatory vocabulary that cells use to manage their liquid organelles.

The therapeutic implications are considerable. Most ALS drug development has targeted downstream events, such as oxidative stress, excitotoxicity or the aggregates themselves. The framework laid out by the Nara Medical University team suggests an upstream strategy: preserve or restore condensate homeostasis. Enhancing chaperone activity, boosting nuclear import, supporting proteostasis components or mimicking the polymer-capping behavior of zinc finger domains could all, in principle, keep pathological proteins in their reversible, harmless state before fibrils ever form. Because the same regulatory principles appear to govern TDP-43, FUS and C9ORF72-related pathology, a therapy aimed at condensate homeostasis might cut across the genetic subtypes of the disease rather than addressing them one by one.

Cautious optimism is warranted. The review is a synthesis of mechanistic studies rather than a demonstration of efficacy in patients, and the authors themselves frame their conclusions as a model to be tested: clarifying how chaperones, import receptors, proteostasis enzymes and structured domains operate across ALS-associated proteins remains the task ahead. Yet the conceptual shift is hard to overstate. ALS, on this view, is not merely a disease of misfolded proteins but a disease of lost reversibility, in which the cell’s capacity to keep its own internal liquids liquid has been eroded. Understanding and reinforcing that capacity may prove to be one of the most promising directions in the search for effective treatments.

Subject of Research: Regulation of biological phase separation by molecular chaperones and related factors in amyotrophic lateral sclerosis

Article Title: Regulation of biological phase separation by molecular chaperones and related factors in amyotrophic lateral sclerosis

Article References: Iguchi, N., Isozumi, N., Sugie, K., & Mori, E. (2026). Regulation of biological phase separation by molecular chaperones and related factors in amyotrophic lateral sclerosis. BMC Medicine. https://doi.org/10.1186/s12916-026-05261-5

Image Credits: AI Generated

DOI: 10.1186/s12916-026-05261-5

Keywords: amyotrophic lateral sclerosis, phase separation, molecular chaperones, TDP-43, FUS, C9ORF72, nuclear import, proteostasis, protein aggregation, RNA-binding proteins, zinc finger domains, condensates