bims-ecemfi 2026-05-24 papers

ACS Nano. 2026 May 19.

Sign of Lateral Curvature Governs Collective Epithelial Migration via Actomyosin Cable Stabilization.

Swati Tanwar, Lintong Wu, Matthew Pittman, Le Liang, Yun Chen, Ishan Barman.

Epithelial tissues migrate collectively across complex geometric landscapes during development, repair, and disease, yet how the sign of substrate curvature directs collective migration remains unclear. Here, we introduce a micropatterned gold platform that presents well-defined lateral curvature cues and use it to dissect curvature-guided epithelial migration. We show that epithelial sheets exhibit a pronounced migration hierarchy, advancing preferentially along convex curvatures while delaying migration from concave regions. Convex curvature stabilizes a continuous, tension-bearing actomyosin cable at the migrating front, enabling rapid and coordinated advancement. In contrast, concave curvature destabilizes this architecture, leading to delayed migration and the emergence of lamellipodia-driven protrusive behavior, particularly near geometric inflection points. Concomitantly, cell-cell junctions along convex regions display elevated E-cadherin levels, indicating curvature-dependent reinforcement of intercellular adhesion that supports collective force transmission. Together, these results identify lateral curvature sign as a geometric control parameter that governs collective epithelial migration by coordinating cytoskeletal organization and cell-cell adhesion. This work establishes surface curvature as a cell-instructive material cue and provides design principles for biomaterials that regulate tissue migration and regeneration.

Keywords: E-cadherin; F-actin cable; cell migration; cell patterning; curvatures; geometric cues

DOI: https://doi.org/10.1021/acsnano.6c03462

Soft Matter. 2026 May 22.

Cooperative effect of local active stresses on the macroscopic contractility of elastic fiber networks.

Abhinav Kumar, David A Quint, Kinjal Dasbiswas.

The collective action of actively contractile units embedded in elastic biopolymer networks plays a crucial role in regulating the network's macroscopic mechanical response. Here, we investigate how the macroscopic boundary stress in model elastic fiber networks depends on the number and nature of embedded contractile units, each exerting an isotropic force dipole, as well as on the bending stiffness of fibers. We find that the macroscopic stress increases nonlinearly with the number of dipoles due to mutual stiffening of initially soft, bending-dominated networks. Using effective medium theory, we relate this enhanced contractility to an increase in the effective average network coordination number due to constraints imposed by the force dipoles. By comparing three distinct force dipole models that differ in their local structures, we demonstrate that the specific manner in which an active unit constrains the network strongly influences the onset and nature of the stiffening transition. Our results highlight that not only the quantity but also the local geometry of force-generating units critically determines the macroscopic mechanical behavior. This framework provides a physical basis for understanding how biological systems-such as molecular motors in the cytoskeleton, or adherent cells in the extracellular matrix-can modulate network-scale nonlinear elastic properties through local tuning of active force-generating units.

DOI: https://doi.org/10.1039/d5sm00803d

bioRxiv. 2026 May 06. pii: 2026.05.01.722023. [Epub ahead of print]

An agent-based model suggests how senescent cell behavior and matrix mechanics drive pulmonary fibrosis in aged mice.

Mackenzie L Skelton, Julie Leonard-Duke, Leilani R Astrab, Joshua A Goedert, Riley T Hannan, Shayn M Peirce, Jeffrey M Sturek, Steven R Caliari.

Idiopathic pulmonary fibrosis (IPF) is a progressive and ultimately fatal disease of aging, driven by dysregulated fibroblast activation and accompanied by collagen accumulation in the lung interstitium, resulting in tissue stiffening. While the accumulation of senescent cells has been increasingly implicated in IPF pathogenesis, understanding the reciprocal dynamics of senescent fibroblast levels and evolving tissue mechanics is difficult to achieve with experimental approaches alone. To address this limitation, we developed an agent-based model (ABM) of fibroblast activation in the lung that couples cell behavior to the dynamic mechanical changes accompanying fibrosis. This model was parameterized entirely from experimental data in young mice to enable robust validation and then adapted to fit aged mouse biology for additional validation. Both young and aged models accurately reflected changes in collagen accumulation and stiffness burden of experimental systems. We then incorporated senescent cell behavior into the aged model to investigate how senescent cell burden influences fibrosis progression and how cell-cell interactions drive senescent cell accumulation. These simulations identified a unique role for juxtacrine-mediated contact between non-senescent and senescent fibroblasts in expanding the total senescent cell burden. Our ABM also revealed that the timing of immune-mediated senescent cell clearance critically regulates fibrotic outcomes. Together, this ABM provides useful insights into how the interrelated dynamics of tissue mechanics and senescent fibroblasts drive fibrosis progression.

DOI: https://doi.org/10.64898/2026.05.01.722023

bioRxiv. 2026 May 08. pii: 2026.05.05.722048. [Epub ahead of print]

Defining characteristics of mesenchymal stem cell-derived matrix-bound nanovesicles compared to conditioned culture medium extracellular vesicles.

Renata Dos Reis Marques, Maulee Sheth, Ava I Salami, Supasek Kongsomros, Leyla Esfandiari, Marley J Dewey.

Matrix-bound nanovesicles (MBVs) are a type of small extracellular vesicle (EV) embedded in the extracellular matrix (ECM) throughout the body. MBVs have been previously isolated from various tissues and in vitro- cultured cell sheets, demonstrating remarkable attributes in regenerative medicine. However, differences between MBVs and conditioned culture medium-derived EVs (liquid-EVs) have yet to be characterized, and the field currently lacks specific protein markers that can identify MBVs from other EV subtypes. Here, we isolate MBVs and liquid-EVs from bone marrow mesenchymal stem cell (MSC) sheets and define differences in size, protein, and zeta potential between these EVs. We show that there is a correlation between cell-driven ECM deposition and MBV and liquid-EV production. We also find that MBVs are smaller, contain less protein per particle, and possess lower zeta potential than liquid-EVs. Interestingly, MBVs also comprise a distinct tetraspanin profile compared to liquid-EVs, with MBVs containing more CD63 and little to no CD81. Finally, we define that CD63, LAMP1, Alix, ITGβ1, and GRP94 and their abundance, may be markers specifically used to identify MBVs from liquid-EVs. Our study paves the way for the characteristic differentiation between MBVs from liquid-EVs, elucidates their differences in biogenesis, and reveals a potential connection between EV and ECM production.

DOI: https://doi.org/10.64898/2026.05.05.722048

Acta Biomater. 2026 May 19. pii: S1742-7061(26)00294-1. [Epub ahead of print]

Effective porosity and fluid flow in macroporous ultrasoft hydrogels: An experimental characterization.

Manuel P Kainz, Michele Terzano, Dagmar Kolb, Gerhard A Holzapfel.

Hydrogels are the preferred materials for applications mimicking soft tissues due to their high water content and tunable mechanical properties. The state of the water in these hydrated networks governs their response to mechanical loading through coupled interstitial flow and large deformations of the solid network. Reliable experimental methods for quantifying the fraction of mobile fluid during mechanical deformation remain limited. Within the theoretical framework of mixture theory, we describe hydrogels as hydrated biphasic media consisting of a deformable incompressible solid matrix and a mobile fluid phase. We developed a mechanical testing protocol that enables the experimental separation of solid and fluid contributions under loading. The method is demonstrated using biocompatible and highly versatile hydrogel phantoms of varying compositions. Controlled, incremental drained confined compression of the hydrogel samples results in free-water fractions of approximately 40%, 60%, and 77%, reflecting the systematic influence of the polymer content on the porosity and fluid mobility. Comparison with cryo-SEM-derived surface porosity reveals statistically significant differences and highlights the scale-dependent sensitivity of surface measurements compared to bulk measurements. This study introduces a new mechanical method for quantifying the free-water fraction in macroporous, ultrasoft, highly hydrated biomaterials. Furthermore, the multi-step protocols enable the separation of dissipative, fluid-related relaxation from the equilibrium response of the solid skeleton, allowing direct calibration of constitutive models for macroporous soft solids. The proposed method provides a reliable basis for the development and optimization of hydrogels for applications where fluid transport is critical, such as neural interfaces, bioelectronic platforms, and tissue-engineered constructs. Statement of significance Water in hydrogels strongly determines their mechanical and transport behaviors, but quantitative measures of the mobile fluid fraction are lacking. We developed a new mechanical testing protocol that enables the experimental separation of solid and fluid contributions under loading in ultrasoft macroporous biomaterials. Validated on different phase-templated composite hydrogels and benchmarked against cryo-SEM-derived porosity, the method provides an experimentally derived effective porosity that can be used in biphasic constitutive models. This work bridges imaging and continuum modeling, with the goal of improving predictive simulations and informing design choices. Furthermore, it serves as basis to optimize the engineering of soft devices used for controlled fluid delivery, responsive scaffolds, and surface-conforming interfaces.

Keywords: Free water; Hydrogels; Porosity; Porous media; Soft biomaterials

DOI: https://doi.org/10.1016/j.actbio.2026.05.009

bioRxiv. 2026 May 07. pii: 2026.05.04.722723. [Epub ahead of print]

Magnetoactive hydrogels to probe curvature-directed endothelial cell mechanosensing.

Avinava Roy, Grace K Hinds, Joshua Yu-Chung Liu, Rishab Yanala, Arina Velieva, Claudia Loebel.

The vascular system exhibits complex, non-planar geometries that become further distorted during pathological remodeling, including arterial tortuosity and aneurysms. Although hemodynamic shear stress is a well-established regulator of vascular function, the direct effects of curvature as an intrinsic geometric cue remain poorly defined. This is largely because existing in vitro models are static and fail to capture the dynamic changes that accompany disease progression. To address this gap, we used a magnetoactive hydrogel platform that enables real-time, on-demand curvature of endothelial monolayers to reproduce clinically established tortuosity metrics. Using this system, we found that elevated curvature increased nuclear localization of yes-associated protein (YAP), with the strongest response in convex relative to concave regions of highly tortuous endothelial monolayers. This mechanosensitive response was accompanied by reduced VE-Cadherin junctional thickness and increased membrane localization of endothelial nitric oxide synthase. Together, these findings identify local curvature, independent of shear stress, as a regulator of endothelial cell mechanosensing and function, and establish a dynamic hydrogel platform for isolating geometric regulation from shear stress inputs in vascular mechanobiology.

DOI: https://doi.org/10.64898/2026.05.04.722723

Commun Biol. 2026 May 21.

Pan-cancer analysis of single-cell profiles with polygenic signals reveals genetic influences on tumor immunity across cancers.

Chunyu Deng, Ka Li, Yunlong Ma, Jingjing Li, Yu Li, Mu Su, Yijun Zhou, Yaru Zhang, Jianzhong Su, Yan Zhang.

Inherited genetic variation can weaken the ability of the immune system to detect and eliminate malignant cells, limiting the effectiveness of cancer immunotherapy. However, how germline polymorphisms shape the tumor immune microenvironment across cancers remains unclear. Here, we present a polygenic analysis framework that integrates single-cell RNA sequencing with GWAS summary statistics across 14 cancer types to identify genes, immune cells, and functional programs linked to cancer risk. We identify three major genetic modules associated with T cells, B cells, and myeloid cells, and show that the T-cell module is strongly linked to cytotoxic and regulatory T cells, particularly in melanoma and breast cancer. We also identify trait-related genes, including CST7, that are associated with cytokine signaling and antigen presentation. In addition, we develop a deep-learning model that predicts immunotherapy response from both tissue and blood samples, supporting the potential of integrated germline and immune features as predictive biomarkers. Together, these findings provide a framework for understanding how inherited variation shapes tumor immunity and may guide biomarker development for cancer immunotherapy.

DOI: https://doi.org/10.1038/s42003-026-10158-3