The cytoskeleton, an intracellular lattice composed of protein fibers such as microtubules and actin filaments, orchestrates essential cellular processes, including shape maintenance, intracellular transport, and motility. Traditional in vitro models used to investigate these networks often rely on chemically modified biomolecules to induce self-organization under illumination, risks altering their native functionalities and thereby complicating biological interpretations. By contrast, the Osaka-based team’s laser-based strategy leverages optical forces to manipulate unaltered tubulin molecules directly, preserving their biological integrity and enabling more physiologically relevant studies.

At the heart of this innovative method lies the principle of optical trapping or optical tweezing, where the electric field gradient created by a tightly focused laser beam exerts forces on dielectric particles at the molecular scale. These forces induce the localized accumulation of tubulin proteins at the laser focus, effectively concentrating the monomers without physical contact. Such accumulation promotes nucleation and polymerization of microtubules, resulting in highly ordered fiber assemblies that exhibit a range of dynamic behaviors analogous to those observed in living cells. The technique, remarkably, relies on near-infrared wavelengths which minimize photodamage and circumvent interference during fluorescence imaging.

The formations observed display a spectrum of motion including radial expansion, bundling into thick fibrils, and even flagella-like rotational behaviors powered by motor proteins and chemical energy within the system. This dynamic activity mimics cellular motility mechanisms and provides unprecedented insight into the structure-function relationship inherent in cytoskeletal dynamics. The ability to control both the localization and the temporal development of these networks with submicrometer precision heralds significant advances in cell biology, biophysics, and biomaterial engineering.

One of the most significant technical advantages of this approach is its non-invasive nature. Unlike existing methods that necessitate chemical tagging or photoactivatable proteins, the laser technique leaves protein functionality intact, which is crucial for accurate modeling of physiological conditions. Furthermore, the compatibility of near-infrared excitation with standard fluorescence imaging modalities enables simultaneous visualization and manipulation, overcoming a longstanding barrier in cellular biophysics research.

The implications of this research extend well beyond fundamental cell biology. By enabling customizable protein fiber architectures, this optical assembly technique offers a platform for engineering novel biomimetic actuators or “robotic muscles.” These protein-based devices could harness the mechanical work of motor proteins to perform controllable movements, paving the way for breakthroughs in soft robotics and nanoengineering. The precise spatiotemporal patterning of protein assemblies could also contribute to the development of advanced biomaterials with tunable mechanical and dynamic properties.

Moreover, the new method opens fresh avenues to dissect the mechanistic underpinnings of crucial cellular phenomena regulated by the cytoskeleton. Processes like cell division, migration, and adhesion rely heavily on orchestrated cytoskeletal dynamics. With this laser-enabled control, researchers can now systematically modulate network structures and study their impact on cell function, revealing deeper insights into disease states where cytoskeletal dysfunction plays a pivotal role, such as cancer metastasis and neurodegenerative conditions.

The research, detailed in the journal Advanced Science, offers a pivotal tool for the scientific community, bridging gaps between theoretical models and experimentally accessible systems. Its ability to reproduce and manipulate complex, dynamic protein fiber networks heralds a paradigm shift in how we explore life’s molecular machinery. By integrating physical optics with molecular biology, this interdisciplinary breakthrough epitomizes the innovative spirit required to unlock new frontiers in science.

Lead author Hiroshi Yoshikawa emphasizes that these advances stem not only from the refined control of protein assemblies but also from minimizing external perturbations. “This method significantly reduces artifacts associated with chemical modification or high-energy light exposure. Our approach allows for the preservation of native protein function and compatibility with live-cell imaging, which is essential for translating findings into biological contexts.”

Beyond the laboratory, the approach signifies a major step towards real-time, in situ manipulation of cellular components, potentially enabling targeted therapeutic interventions at the molecular level. For example, directing or disrupting specific cytoskeletal arrangements on demand could be leveraged to influence cell behavior in regenerative medicine or cancer treatment. The laser’s precision offers a non-contact modality with potential for scalability and integration into microfluidic systems.

This work is supported by prestigious funding bodies including the Japan Society for the Promotion of Science and the Japan Science and Technology Agency, reflecting its high scientific and technological merit. As researchers refine the technique and further unravel the complexities of protein fiber dynamics, the intersection of optics, biophysics, and cellular biology promises fertile ground for new discoveries.

In summary, the pioneering use of photophysical effects induced by a tightly focused laser beam to fabricate dynamic protein fiber assemblies marks a transformative development within molecular and cellular biophysics. This innovative strategy enables unmatched spatiotemporal control over microtubule organization while preserving native protein function. The resulting dynamic assemblies recreate key aspects of cytoskeletal behavior and propel advances in both fundamental biology and applied fields such as biomaterials and soft robotics, highlighting the profound potential of integrating optical physics with life sciences.

Subject of Research: Not applicable

Article Title: Spatiotemporal Control of Formation of Dynamic Protein Fiber Assemblies via Photophysical Effects of a Focused Laser Beam

News Publication Date: 18-May-2026

References:
Hiroshi Y. Yoshikawa et al., “Spatiotemporal Control of Formation of Dynamic Protein Fiber Assemblies via Photophysical Effects of a Focused Laser Beam,” Advanced Science, DOI: 10.1002/advs.75531

Image Credits: 2026, Hiroshi Y. Yoshikawa et al., Spatiotemporal Control of Formation of Dynamic Protein Fiber Assemblies via Photophysical Effects of a Focused Laser Beam, Advanced Science

Keywords

Physics, Cytoskeletal proteins, Optics, Optical trapping, Photonics

In a pioneering study led by Professor Nobutaka Hirokawa of Juntendo University in Tokyo, alongside collaborators from the University of Tokyo and Gunma University, groundbreaking atomic-level insights into kinesin-2’s cargo recognition machinery have been unveiled. Utilizing a combination of cryo-electron microscopy and molecular dynamics simulations, the structural architecture of the kinesin-2 heterotrimeric complex—composed of KIF3A, KIF3B, and KAP3 subunits—was resolved in unprecedented detail, particularly focusing on its interaction with the adenomatous polyposis coli (APC) protein, a cargo essential for neuronal RNA transport and tumor suppression.

Central to this breakthrough is the identification of a previously unknown structural motif in the kinesin-2 tail domain, coined the hook-like adaptor and cargo-binding (HAC) domain. This domain comprises a distinctive helix–β-hairpin–helix (H-βh-H) configuration that forms a highly specialized scaffold, enabling the cooperative assembly of adaptor proteins, notably KAP3, alongside cargo recognition. The HAC domain acts analogously to a molecular hook, a precise connector that orchestrates the selective engagement and transport of cargo within the dense cellular environment.

Professor Hirokawa emphasizes that the discovery of the HAC domain marks a significant leap in decoding the molecular logistics system inside neurons. “Our findings reveal the crucial structural basis by which kinesin-2 motors meticulously recognize and transport specific cargos, a process that had defied molecular characterization until now,” he stated. This insight not only illuminates the sophisticated specificity of motor-cargo interactions but also elucidates how these transport processes are finely orchestrated to maintain neuronal function.

Elaborating on the mechanism, the study identified four distinct binding interfaces between the kinesin-2 complex and the KAP3 adaptor protein. Notably, the KIF3A subunit emerged as the primary driver for cargo binding, contributing the majority of the binding energy, whereas KIF3B provides essential structural support. This delineation of functional roles within the motor complex underscores a nuanced division of labor, ensuring stable yet flexible cargo attachment necessary for dynamic intracellular trafficking.

Furthermore, the HAC/KAP3 binding configuration shares structural resemblance with known cargo-binding regions from other motor proteins such as dynein and kinesin-1, suggesting the existence of a conserved cargo recognition framework across diverse motor systems. This revelation hints at an evolutionary convergence whereby molecular “hooks” have evolved as a universal solution for targeted cargo delivery, highlighting the fundamental nature of such adaptor-mediated specificity in cellular logistics.

Validating their structural model through complementary cross-linking mass spectrometry experiments and biochemical assays, the researchers confirmed that the HAC domain selectively engages with the ARM repeat region of APC. This interaction is critical for the transport of neuronal RNA cargo, demonstrating that disruptions in this process could have profound cellular consequences. Such specificity is vital for neuronal health, given that misregulation of cargo transport systems has been implicated in a multitude of neurodegenerative and neurodevelopmental disorders.

The authors also emphasize the broader biomedical implications of this discovery. Intracellular transport defects are increasingly recognized as a molecular underpinning for various ciliopathies, neurodegenerative diseases such as Alzheimer’s and Parkinson’s, and other neurological dysfunctions. Greater understanding of how kinesin-2 motors decipher their cargo “address” opens potential avenues for targeted drug design. By modulating motor-cargo interfaces or adaptor assembly processes, it could be possible to rectify transport defects or selectively interfere with pathogenic cargo trafficking pathways.

Beyond therapeutic prospects, this research heralds exciting possibilities in the field of synthetic biology. The detailed molecular blueprint of the HAC domain and its adaptor assembly offers a foundation for engineering artificial transport systems capable of mimicking the exquisite precision of natural intracellular logistics. Such biomimetic designs could revolutionize drug delivery, biosensing, and even nanoscale manufacturing platforms by leveraging engineered molecular motors with programmable cargo specificity.

Despite the monumental progress, the authors acknowledge remaining challenges. Certain regions within the kinesin-2 complex, particularly flexible segments, resisted structural resolution due to inherent conformational dynamics. Moreover, the diversity of cargos beyond APC and potential regulatory mechanisms modulating HAC domain interactions warrant further investigation to fully map the kinesin-2 transport repertoire within various cell types and physiological contexts.

The journey of kinesin research, which Professor Hirokawa’s lab pioneered since the 1980s by first identifying the kinesin superfamily and elucidating their motility along cytoskeletal highways, has now entered a new era. By decoding the atomic-scale “logistics code” that enables cargo recognition, this study transforms our comprehension of cellular transport from descriptive to mechanistic, promising to illuminate how molecular machines drive life’s essential logistics in health and disease.

As neurons rely on precise cargo delivery for normal function and survival, this study’s insights into the HAC domain unlock potential to understand—and eventually manipulate—the cellular highways that sustain brain health. The fusion of structural biology, biochemistry, and cell biology in this research exemplifies the integrative approach necessary to unravel the complexities of intracellular transport and pave the way for novel diagnostics and therapeutics in neurobiology.

The identification of the HAC domain thus represents a landmark finding that not only resolves a long-standing mystery in cell biology but also lays the conceptual and practical groundwork for future innovations spanning medicine, synthetic engineering, and fundamental neuroscience. This molecular “hook” imagery captures the elegant specificity by which kinesin-2 motors navigate cellular landscapes, inspiring new perspectives on the logistical precision inherent to life itself.

Subject of Research: Cells

Article Title: The hook-like adaptor and cargo-binding (HAC) domain in the kinesin-2 tail enables adaptor assembly and cargo recognition

News Publication Date: 24-Oct-2025

Web References:
https://doi.org/10.1126/sciadv.ady5861

References:
Xuguang Jiang, Radostin Danev, Sotaro Ichinose, Baichun Niu, Sumio Ohtsuki, Haruaki Yanagisawa, Satoru Nagatoishi, Kouhei Tsumoto, Nobutaka Hirokawa, and Masahide Kikkawa. “The hook-like adaptor and cargo-binding (HAC) domain in the kinesin-2 tail enables adaptor assembly and cargo recognition.” Science Advances, 24 October 2025. DOI: 10.1126/sciadv.ady5861

Image Credits: Professor Nobutaka Hirokawa from Juntendo University, Japan

Keywords: Intracellular transport, Cell biology, Molecular biology, Protein structure, Neurodegenerative diseases

The liver is an exceptional organ that performs a wide array of functions essential for maintaining metabolic homeostasis. Among its numerous roles, the liver is central to lipid metabolism, glucose homeostasis, and toxin detoxification. However, disruptions to these functions often lead to various liver diseases, with MAFLD being particularly prevalent. In this context, understanding the underlying molecular mechanisms becomes crucial for developing effective interventions.

KIF13B is a type of kinesin motor protein that plays a critical role in intracellular transport. This protein is known for its ability to transport various cargoes, including organelles and signaling molecules, along microtubules within cells. Previous studies have highlighted KIF13B’s significance in neuronal function and proliferation, but its involvement in liver metabolism had remained largely unexplored until now.

By employing a combination of genetic, biochemical, and physiological approaches, the research team investigated the specific functions of KIF13B in hepatocytes, the primary cells of the liver. Through carefully designed experiments, they demonstrated that KIF13B facilitates the transport of key metabolic enzymes and signaling molecules, which are crucial for maintaining normal hepatic function.

One of the most striking findings of the study is KIF13B’s ability to regulate the localization of pivotal enzymes involved in lipid metabolism. When KIF13B activity was disrupted, the researchers observed a significant alteration in the distribution of these enzymes, leading to impaired lipid processing in hepatocytes. This disruption could result in the accumulation of lipids within liver cells, a hallmark of fatty liver disease.

The team also revealed that KIF13B influences the liver’s response to insulin, a key hormone in glucose metabolism. In their experiments, they found that the disruption of KIF13B led to insulin resistance in hepatocytes, a condition often precursor to type 2 diabetes and metabolic syndrome. This discovery elucidates a critical pathway by which KIF13B exerts its influence over liver metabolism and suggests that enhancing its function might hold therapeutic potential for treating these interconnected metabolic disorders.

Moreover, the research highlighted the interaction between KIF13B and other cellular signaling pathways. The team identified that KIF13B plays a role in the activation of AMP-activated protein kinase (AMPK), a master regulator of energy metabolism. AMPK activation is essential for maintaining energy balance and promotes processes such as fatty acid oxidation while suppressing lipogenesis. Thus, KIF13B’s influence on AMPK signaling provides another layer of complexity to its role in maintaining hepatic metabolism.

These findings have significant implications for understanding MAFLD and metabolic syndrome. Given the increasing prevalence of these conditions associated with lifestyle factors such as obesity and physical inactivity, targeting KIF13B could represent a novel approach to therapeutic development. By restoring the normal function of this motor protein, it may be possible to mitigate the pathogenic processes underlying these diseases.

Furthermore, this discovery could spark interest in the development of KIF13B modulators as a new class of pharmacological agents to combat metabolic dysfunction. Potential therapeutic strategies could involve small molecules designed to enhance KIF13B activity or gene therapy approaches aimed at correcting KIF13B deficiencies in hepatocytes.

The study’s results also prompt further investigation into the broader implications of motor protein functions in other organs and systems. Given the interconnected nature of metabolic processes, exploring the role of KIF13B beyond the liver could yield insights into how motor proteins influence systemic metabolism and contribute to other metabolic disorders.

As the research community absorbs these findings, there is considerable enthusiasm for the potential application of this knowledge in clinical settings. Investigations into the therapeutic targeting of KIF13B could ignite new avenues for treatment and prevention of MAFLD and its associated complications. As the global burden of metabolic diseases continues to rise, such innovative research is vital for developing effective strategies to improve patient outcomes and reduce healthcare costs.

In conclusion, the work of Miao et al. marks a significant advancement in our understanding of the molecular mechanisms underlying hepatic metabolism and the regulation of liver disease. Identifying KIF13B as a key player in this intricate network opens the door to novel therapeutic strategies that could ultimately lead to better management of metabolic dysfunction-associated fatty liver disease, providing hope for millions affected by this debilitating condition.

Subject of Research:

Article Title: Motor protein KIF13B orchestrates hepatic metabolism to prevent metabolic dysfunction-associated fatty liver disease

Article References:

Miao, GL., Zhang, WX., Xu, YT. et al. Motor protein KIF13B orchestrates hepatic metabolism to prevent metabolic dysfunction-associated fatty liver disease.
Military Med Res 12, 11 (2025). https://doi.org/10.1186/s40779-025-00594-3

Image Credits: AI Generated

DOI:

Keywords: KIF13B, hepatic metabolism, motor protein, fatty liver disease, metabolic dysfunction.

The cytoskeleton in contemporary eukaryotic cells is a marvel of biological engineering. It consists primarily of three filamentous structures: actin filaments, microtubules, and intermediate filaments. Together, these protein constituents confer shape, facilitate intracellular transport, power motility, and orchestrate critical processes like cell division. While this system’s sophistication is well-established, the evolutionary origins of its constituent proteins—how ancient microbes gave rise to such complexity—have remained elusive. The new research from IISc offers compelling biochemical and structural evidence tracing this evolutionary journey back to archaea, a domain of life once thought too simple to harbor such complexity.

Central to these revelations is a group of microbes known as Asgard archaea, discovered in some of the planet’s most extreme environments, including deep-ocean sediments. Genomic studies have previously hinted that these archaea are the closest known relatives of all modern eukaryotes. Intriguingly, Asgard archaea possess genes encoding proteins akin to those of the eukaryotic cytoskeleton, potentially representing transitional evolutionary stages. Leveraging these connections, the IISc-led team collaborated with notable institutions such as IISER Pune, NCBS, and NISER to dissect the molecular characteristics of two paralogous proteins from an Asgard member, Odinarchaeota yellowstonii.

Odinarchaeota yellowstonii—named after the Norse god Odin and isolated from Yellowstone National Park—supplies a remarkable window into early cytoskeletal evolution. The team focused on two FtsZ paralogs, FtsZ1 and FtsZ2, both belonging to a protein family ancestral to tubulin, the key building block of eukaryotic microtubules. These proteins, crucial for bacterial cell division, had been largely unexplored in Asgard archaea, making their study a pivotal endeavor to understand cytoskeletal origins.

Through sophisticated biochemical assays and cutting-edge cryo-electron microscopy techniques, the researchers unveiled that OdinFtsZ1 and OdinFtsZ2 exhibit distinct assembly behaviors. OdinFtsZ1 polymerizes into curved single filaments, reminiscent of the contractile rings formed by bacterial FtsZ during cytokinesis. In stark contrast, OdinFtsZ2 spontaneously assembles into stacked spiral rings, structures that strikingly resemble primitive microtubule-like tubules. This differentiation in filament morphology provides a smoking gun for the evolution of cytoskeletal diversity from simpler ancestral forms.

Beyond their structural differences, these proteins exhibit unique modes of membrane attachment, signifying an early division of functional labor seldom documented in prokaryotic cells. OdinFtsZ1 anchors to the cell membrane directly through a helical tail, whereas OdinFtsZ2 utilizes an adaptor protein for indirect tethering. This nuanced specialization implies a primordial cooperation between cytoskeletal elements, foreshadowing the intricate interplay observed among filament systems in extant eukaryotes.

The complexity observed in modern cytoskeletal networks is believed to have evolved through gene duplication events, followed by functional divergence and enhanced cooperation between different filament types. The discoveries detailed in this study strongly support the hypothesis that these evolutionary processes had already commenced in Asgard archaea, positioning these organisms as living archives of the cellular innovations that paved the way for eukaryotic life.

The dual nature of FtsZ paralogs in Odinarchaeota thus captures a crucial evolutionary snapshot—a transitional interface where simple microbial filaments began to diversify and specialize, assembling into multifunctional frameworks. Such insights bridge a gap in our understanding of how the cytoskeleton’s molecular complexity arose, shedding light on the cellular mechanisms facilitating the emergence of structural dynamism and intracellular organization.

Looking forward, the research group aims to culture Asgard archaea in laboratory settings, a pursuit that would enable direct cellular observations of these ancient proteins in vivo. Such experimentation holds the potential to revolutionize our comprehension of early cytoskeletal operation and elucidate how these foundational filaments influenced the advent of complex cellular life.

Saravanan Palani, Assistant Professor of Biochemistry at IISc and corresponding author of the study, emphasizes the evolutionary ramifications of their findings: “These proteins preserve a snapshot of an ancient transition. They connect the threads of history between the simplest microbial filaments and the dynamic scaffolds that sustain all higher organisms.” This conceptual framework transforms our understanding of cellular evolution, suggesting that the sophisticated eukaryotic cytoskeleton emerged not abruptly but gradually from simpler ancestral elements in the microbial world.

This research not only redefines molecular evolutionary timelines but also underscores the profound continuity of life, tracing complex cellular architectures back to the depths of Earth’s microbial past. The findings, by revealing how diverse filament morphologies and membrane associations began to take shape early in evolutionary history, invite a reconsideration of how life’s cellular machinery evolved to its present-day intricacy.

In sum, the molecular investigation of Odinarchaeota’s FtsZ paralogs marks a landmark step toward deciphering the cytoskeleton’s origins. By illuminating the early morphological and functional diversification of cytoskeletal proteins, this work provides a vital piece to the grand evolutionary puzzle that defines life’s transition from simplicity to complexity.

Subject of Research: Evolution of cytoskeletal proteins in Asgard archaea, focusing on filament morphology and membrane tethering in FtsZ paralogs.

Article Title: Distinct filament morphology and membrane tethering features of the dual FtsZ paralogs in Odinarchaeota

News Publication Date: 8-Aug-2025

Web References:
https://doi.org/10.1038/s44318-025-00529-7

Image Credits: Saravanan Palani lab, made using BioRender

Keywords:
cytoskeleton, Asgard archaea, Odinarchaeota, FtsZ paralogs, microtubule evolution, tubulin, cryo-electron microscopy, membrane tethering, cytoskeletal evolution, ancient microbes, eukaryotic cells, cell division