The study, published in Advanced Science, tackles a problem that has frustrated the field for years. Researchers have extensively studied how nanoparticle size, shape, and surface chemistry influence transport through mucus, but two factors have remained comparatively neglected: the mechanical flexibility of the particle itself, and the biological variability of the mucus barrier across different organs and physiological states. The difficulty is that flexibility is nearly impossible to tune in isolation. Modifying a particle’s mechanical properties typically changes its geometry or surface chemistry at the same time, making it hard to know whether observed effects stem from deformability or from some other confounding variable.

DNA origami offered a way out of this impasse. The technique folds a long single-stranded DNA scaffold, in this case from the M13mp18 bacteriophage, using hundreds of short complementary staple strands into precisely defined nanoscale shapes. The researchers built a rod-shaped structure called a 14-helix bundle, roughly 150 nanometers long—a size deliberately chosen to match the reported mesh size of mucus, which ranges from about 100 to 200 nanometers. By selectively removing staples from a central hinge region, the team could systematically increase the structure’s bending flexibility while keeping its overall dimensions and surface chemistry essentially unchanged.

The result was a family of five variants, designated Hinge 0 through Hinge 4, ranging from fully rigid to maximally flexible. Transmission electron microscopy confirmed that all five assembled correctly and retained their rod-like geometry, with only modest and statistically insignificant differences in effective length. The bending angles told a clear story: the rigid Hinge 0 structures remained nearly linear at close to 180 degrees, while the most flexible Hinge 4 constructs averaged around 120 degrees, with individual particles bending as far as 75 degrees. The most compliant designs also showed pronounced twisting, a sign of increased rotational freedom.

Before introducing the structures to biological samples, the team measured their diffusion in simple buffer and in a viscous polyethylene glycol solution that mimics mucus’s viscosity without any specific biochemical interactions. In both inert environments, flexibility paid off. The most flexible rods diffused roughly 45 percent faster than the rigid ones in buffer, and about 48 percent faster in the viscous medium. The explanation is hydrodynamic: bending and shape fluctuations reduce the effective drag a rod experiences as it moves through fluid, making it easier to translate forward even before any biological interactions come into play.

The real test came in mucus. The researchers tracked fluorescently labeled particles in three physiologically distinct porcine mucus environments: fasted intestinal mucus, fed intestinal mucus, and stomach mucus. In fasted intestinal mucus, the trend from the inert media held—more flexible rods moved farther and faster than rigid ones, supporting the idea that deformability helps particles squeeze through the sterically heterogeneous mucus mesh. Surprisingly, coating the particles with bovine serum albumin, a common surface-passivation strategy, actually reduced diffusion of all variants, likely because the protein layer increases hydrodynamic size and adds steric interactions at the particle-mucus interface. Yet even with this burden, flexible rods retained a measurable advantage over rigid ones.

The other two mucus environments revealed a more complicated picture. Fed intestinal mucus and stomach mucus both slowed particle diffusion overall, suggesting stronger adhesive interactions. To understand why, the team characterized each mucus sample using cryogenic scanning electron microscopy, rheology, and proteomics. The two intestinal samples, regardless of feeding state, looked structurally similar under the microscope, with elongated, oval-shaped pores, while stomach mucus displayed a distinctly different architecture of predominantly circular pores. Rheological measurements confirmed that stomach mucus was significantly stiffer than either intestinal sample. Proteomics identified roughly 6,300 proteins per sample, with about 88 percent shared across all three sources—but stomach mucus contained 258 unique proteins, compared with just 15 and 30 for the fasted and fed intestinal samples.

Single-particle tracking then exposed a critical mechanistic divide that bulk measurements would have missed. In stomach and fasted intestinal mucus, particles moved mostly as individuals, and their transport appeared limited by steric hindrance within the polymer network—conditions under which flexibility clearly helps. In fed intestinal mucus, however, particles clustered into aggregates, indicating that adhesive surface interactions, including electrostatic and hydrophobic binding to mucins, dominated the transport behavior. Under those conditions, adding flexibility alone accomplished little. Instead, BSA passivation was needed first to suppress aggregation and restore mobility—and once that happened, flexibility again provided an additional boost to diffusion. In other words, the right design strategy depends entirely on which barrier mechanism dominates in a given mucus environment.

The team also probed a scenario closer to real oral drug delivery: sequential exposure to intestinal fluid followed by mucus. Particles first incubated in intestinal fluid—a complex soup of enzymes, bile salts, and macromolecules—showed reduced mobility compared with particles introduced directly from buffer, and their subsequent diffusion in mucus was further diminished. Prior work has shown that DNA origami structures remain stable in intestinal mucus, so structural degradation was not the culprit; instead, fluid components appear to alter particle surface properties or create transient binding events that hinder movement. Crucially, the relative advantage of flexible designs persisted even after this fluid preconditioning, suggesting that mechanical compliance remains valuable under physiologically realistic conditions.

The findings carry practical weight for nanomedicine. Widely used surface-passivation strategies such as PEGylation can improve mucus penetration but may simultaneously compromise targeting and cellular uptake, so complementary approaches are needed. By decoupling flexibility from geometry and surface chemistry, this work establishes structural mechanics as a legitimate, independently tunable design parameter for mucosal drug carriers. The authors suggest the principle may extend beyond the gastrointestinal tract to pulmonary, nasal, and cervical mucus, though its impact will always depend on whether a given barrier is governed primarily by mechanical confinement or by surface-driven interactions. The broader message is that rational nanocarrier design demands a mechanistic diagnosis first: identify whether steric obstruction, interfacial adhesion, or aggregation is the limiting factor, and only then choose between flexibility, passivation, or a combination of both.

Subject of Research: Effect of DNA origami mechanical flexibility on nanoparticle transport through gastrointestinal mucus

Article Title: Mechanical Flexibility Enables DNA Origami to Overcome Steric Confinement in Mucus

Article References: Tollemeto, M., Tsang, E., Hong Lin, M. K. T., Mannino, L., Gothelf, K. V., & Boisen, A. (2026). Mechanical Flexibility Enables DNA Origami to Overcome Steric Confinement in Mucus. Advanced Science, 13(55), Article e76493. https://doi.org/10.1002/advs.76493

Image Credits: AI Generated

DOI: 10.1002/advs.76493

Keywords: DNA origami, mucus, nanoparticle transport, drug delivery, mechanical flexibility, single-particle tracking, mucosal barriers, surface passivation, 14-helix bundle, proteomics, rheology, gastrointestinal mucus

The Rice team, drawn from the departments of Chemical and Biomolecular Engineering, Chemistry, and Materials Science and Nanoengineering, along with the Rice Advanced Materials Institute, has developed a relatively soft and flexible porous material that selectively transports lithium ions. The work, published in the peer-reviewed journal Chemical Science, introduces a new design philosophy for porous solid electrolytes, one that treats mechanical adaptability not as an afterthought but as a core performance criterion, sitting alongside ionic conductivity and chemical stability in the designer’s toolkit.

The material at the heart of the study is called ZnBTCA, and it belongs to a family of compounds known as metal-organic frameworks, or MOFs. These are porous crystalline materials built from metal atoms connected by organic molecules into repeating, lattice-like structures. What makes MOFs so compelling for battery applications is their architecture: they contain tiny, ordered channels whose size and chemistry can be tailored to move or hold specific molecules and ions. In principle, a MOF can act as a molecular sieve for charge, allowing lithium ions to stream through its pores while blocking everything else. Many MOFs previously explored as battery electrolytes, however, have been constructed from relatively rigid aromatic linkers — the organic struts that connect the metal nodes — which produce frameworks that are stiff and mechanically unyielding.

ZnBTCA takes a fundamentally different route. Instead of an aromatic linker, it employs a flexible aliphatic linker, an organic molecule with a pliable carbon-chain backbone. That single design choice ripples through the entire material: the framework itself becomes softer and more mechanically adaptable, capable of deforming and conforming rather than resisting. The researchers also emphasized practicality in their selection of building blocks. The material is assembled from relatively abundant, low-cost components, including zinc — one of the most accessible metals in the battery chemist’s repertoire — and an inexpensive aliphatic linker, an important consideration if such materials are ever to move from the laboratory bench toward real-world manufacturing.

First author Zina Deriche, a graduate student in chemical and biomolecular engineering at Rice, framed the shift in thinking that underpins the work. MOF electrolytes, she noted, are often designed primarily around how effectively they transport ions. The Rice study demonstrates that the mechanical properties of the framework can also be an important part of the design equation. It is a deceptively simple reframing, but one with significant consequences: a material that can flex with the battery as it charges and discharges may hold up better over thousands of cycles than one that cracks or delaminates under mechanical stress.

The dual functionality of ZnBTCA is what excites the team most. The material’s flexible molecular building blocks make it relatively soft, while its negatively charged framework structure favors the movement of positively charged lithium ions through its channels. Stavroula Alina Kampouri, a corresponding author of the study and assistant professor across chemical and biomolecular engineering, chemistry, and materials science and nanoengineering, described the convergence of these properties as the most thrilling aspect of the result. The same material, she explained, brings together flexible building blocks that make the framework softer and more adaptable with a negatively charged structure that promotes selective lithium-ion transport. Bringing those properties together, she said, offers a new way to design MOF electrolytes by considering how ions move and how the material behaves mechanically at the same time.

The experimental results lend strong support to the design concept. The researchers first exchanged the sodium ions residing within the framework for lithium ions, a process known as ion exchange that is common in MOF chemistry. After the exchange, they found that roughly 95 percent of the mobile charge-balancing ions in the material were lithium, while the framework itself remained structurally intact — a critical demonstration that the delicate crystalline lattice could survive the swapping of its guest ions without collapsing. Selectivity matters enormously in an electrolyte: a material that carries only lithium ions, rather than a mixed crowd of mobile species, delivers cleaner, more efficient battery operation and helps prevent parasitic reactions that degrade performance over time.

Further electrochemical testing quantified just how selective the material is. In measurements of the current flowing through the material, lithium ions accounted for approximately 79 percent of the total ionic current — a high lithium-ion transference number that indicates the framework’s channels and charged surfaces are indeed preferentially shepherding lithium rather than the counterions left behind by the exchange process. For electrolyte designers, that figure represents a meaningful benchmark, because a high transference number reduces the concentration gradients that build up inside a cell during fast charging and discharging, which in turn improves power delivery and reduces energy losses.

Perhaps the most demanding test the team ran addressed one of the most feared failure modes in next-generation batteries: short circuiting. In lithium-metal batteries, where a strip of pure lithium metal serves as one electrode, repeated charging and discharging can cause lithium to grow unevenly, forming needle-like structures that eventually pierce the electrolyte and create an unwanted electrical pathway — a short circuit that can disable or even ignite a cell. To probe how ZnBTCA would cope with this challenge, the researchers incorporated the material into a solid electrolyte membrane and sandwiched it between two lithium-metal electrodes. The cells then operated stably for nearly 300 hours as the researchers progressively increased the current, with no evidence of short-circuiting under the conditions tested. While laboratory cycling tests are far from the final word on commercial viability, the result suggests that a softer, more conformable electrolyte membrane may help suppress the mechanical pathways through which dendrites typically propagate.

The broader significance of the work lies in the design principle it establishes. To the team’s knowledge, ZnBTCA is the first MOF electrolyte built from an aliphatic linker with a flexible carbon-chain backbone, a distinction that opens an essentially unexplored region of chemical space for electrolyte development. Sibani Lisa Biswal, chair of chemical and biomolecular engineering and the William M. McCardell Professor in Chemical Engineering at Rice, as well as a professor of materials science and nanoengineering, summarized the lesson: researchers can think beyond just the chemistry and pore structure of these materials, because mechanical flexibility can also become a design tool for developing MOF electrolytes for solid-state batteries. The results suggest that mechanical flexibility could take its place alongside chemical composition, pore structure, and framework charge as a tunable parameter in the rational design of battery electrolytes.

The research was supported by a GEM Fellowship as well as the National Science Foundation under grant No. 2404376, and portions of the work used resources of the Shared Equipment Authority at Rice. As solid-state batteries edge closer to commercial reality in electric vehicles, consumer electronics, and grid storage, the challenge is no longer simply finding materials that conduct lithium ions well — it is finding materials that can survive the mechanical realities of a battery’s life. By proving that a MOF can be simultaneously soft, selective, and structurally robust, the Rice team has added a promising new entry to the electrolyte design playbook, and perhaps a hint that the future of the solid-state battery will be built not on rigid crystals, but on frameworks that know how to flex.

Subject of Research: Flexible metal-organic framework electrolytes for selective lithium-ion conduction in solid-state batteries

Article Title: A softer porous material could help improve solid-state batteries

Article References: A softer porous material could help improve solid-state batteries. (n.d.). Original publication

Image Credits: AI Generated

DOI: Not provided

Keywords: solid-state batteries, metal-organic frameworks, lithium-ion transport, ZnBTCA, electrolytes, mechanical flexibility, Rice University, Chemical Science, aliphatic linker, lithium-metal anodes, ion selectivity, energy storage