bims-ecemfi 2026-07-05 papers

bioRxiv. 2026 Jun 25. pii: 2026.06.24.734376. [Epub ahead of print]

Lipid Network Crosslinked Hydrogels: Controlling Material Dynamics Across Multiple Length Scales Through Lipid Movement.

Neil J Baugh, Michelle S Huang, Narelli de Paiva Narciso, Jordan A Bunch, Jayniana Williams, Yueming Liu, Ruby Onsongo, David Kilian, Renato S Navarro, Sarah C Heilshorn.

Control over network dynamics at different length scales is a feature of natural materials challenging to replicate in synthetic hydrogels. Hydrogel viscoelasticity is commonly controlled by tuning the kinetics of reversible crosslinks; however, this strategy inherently links the resulting macroscale and nanoscale dynamics of the individual network components. Taking inspiration from biological materials that feature lipids as structural elements, we introduce Lipid Network Crosslinked (LINC) hydrogels that exploit the mobility of individual lipids within self-assembled liposomes as covalent, network-crosslinking points. These mobile, covalent crosslinks increase hydrogel stress relaxation rates over 20-fold compared to polymer-only hydrogels with equivalent crosslinking chemistries and stiffnesses. We demonstrate that liposome design parameters, including degree of surface functionalization and tail saturation, provide a means to independently control the macroscale storage moduli and stress relaxation behavior. Finally, as an application where control over network dynamics at different length scales is critical, we placed cell-adhesive ligands onto more mobile or less mobile network elements. Human neural progenitor cells cultured within LINC hydrogels of identical macroscale viscoelasticity significantly altered their phenotype in response to nanoscale ligand dynamics. These results establish LINC hydrogels as biomimetic materials that leverage nanoscale lipid mobility within a macroscale polymeric network to control dynamics at multiple length scales.

DOI: https://doi.org/10.64898/2026.06.24.734376

ACS Cent Sci. 2026 Jun 24. 12(6): 777-788

Synthetic Surrogates of Collagen-Rich Microenvironments: Integrating Modular Bioactive Fibrillar Structure and Tunable Viscoelasticity via Multifunctional Assembling Peptides.

Rafael A Castro, Lina Pradhan, Jeffrey Caplan, Caitlin D'Ambrosio, April M Kloxin.

Collagen imparts structure, viscoelasticity, and bioactivity to the extracellular matrix (ECM) with variance between organs and between healthy and diseased states. Synthetic mimics of collagen-rich tissues remain a need in applications, from biological studies to regenerative medicine, for parsing and controlling these properties. We designed multifunctional collagen mimetic peptides (mfCMPs) that self-assemble into triple helices and fibrils and contain integrin binding motifs: GFOGER, a binding site within intact collagen I, and RGD, a cryptic binding site available within denatured collagen I. These mfCMPs are incorporated into hydrogel-based synthetic ECMs to impart collagen-like hierarchical structures, viscoelasticity, and bioactivity with modularity. We establish innovative methods for imaging the resulting nano- and micro-structures within the hydrogel using super-resolution microscopy. The physically assembled mfCMPs impart tunable, concentration-dependent viscoelasticity within otherwise elastic, covalently cross-linked hydrogels, exhibiting relaxation half times over orders of magnitude and similar to soft tissues. Notably, breast cancer cells encapsulated and cultured in synthetic ECMs with a bioactive fibrillar structure and viscoelastic properties formed large, growing spheroids. Overall, these modular building blocks provide an innovative tool for creating fully synthetic surrogates of collagen-rich microenvironments, aiding both fundamental and translational biological studies and providing a framework to imbue tunable viscoelasticity to synthetic ECMs.

DOI: https://doi.org/10.1021/acscentsci.5c02175

Nat Immunol. 2026 Jul 03.

Mechanosensing by T cells promotes a tissue-resident memory transcriptional program.

Cell migration and strategic positioning within tissues is critical for the rapid mobilization of a T cell response. T cells must remain motile in both lymphoid and nonlymphoid tissues, which vary widely in mechanical properties such as stiffness. Here we showed that activated T cells sensed mechanical cues and responded with changes in cell morphology, nuclear envelope composition and initiation of DNA repair to protect their genomic material from force-mediated damage. Increased mechanical input also drove the transcriptional reprogramming of activated T cells, including changes in many of the core genes shared by tissue-resident memory T cells across diverse tissues, by modulating the expression of the tissue-resident memory T cell-associated transcription factors Klf2, Runx3 and Hic1. Thus, mechanosensing by activated T cells impacted T cell fate, promoting a transcriptional program associated with tissue residency.

DOI: https://doi.org/10.1038/s41590-026-02581-9

Nat Mater. 2026 Jul;25(7): 1278-1287

Boundary geometry controls a topological defect transition that determines lumen nucleation in embryonic development.

Pamela C Guruciaga, Takafumi Ichikawa, Steffen Plunder, Takashi Hiiragi, Anna Erzberger.

Topological defects determine the collective properties of anisotropic materials. Nonetheless, it is not fully understood how their configurations are controlled, especially in three dimensions. In living matter, contributions of two-dimensional topological defects to biological functions have been demonstrated, but whether three-dimensional polar defects have any biological relevance is unclear. Here we report a charge-preserving transition between three-dimensional defect configurations driven by boundary geometry and independent of material parameters. Moreover, we find that three-dimensional polar defects in the mouse embryo are the sites where fluid-filled lumina form, essential structures for subsequent development. We validate these findings by experimentally perturbing embryo shape beyond the transition point, which results in the creation of additional lumen initiation sites near predicted defect locations. Overall, our results reveal how boundary geometry controls polar defects, and how embryos use this mechanism for shape-dependent lumen formation. We expect this defect-control principle to apply broadly to systems with orientational order.

DOI: https://doi.org/10.1038/s41563-026-02594-7