Biology subjects

Urena Martin, C.

Publications and source records attributed to Urena Martin, C..

2 recordsLinked to original sources

bioRxiv2025

Heterogeneity in environmental stiffness alone can guide cells and shape tissues

While topographical and chemical cues are well known to regulate cell shape and function, the role of stiffness heterogeneity has remained unclear. Here, we demonstrate - for the first time to our knowledge - that cells can be guided solely by the stiffness heterogeneity of their environment. To that end, we engineered a cell-guiding platform with abrupt, subcellular stiff and soft domains, whose flatness and uniform chemistry eliminated confounding cues. Cells elongate and align along stiff regions, sensing soft domains as barriers when wider than 2 microns. Perturbated myosin activity, cortical tension, and elasticity contrast reveal distinct biomechanical contributions, while a probabilistic model integrating adhesion, contractility, and cortical tension extracts key mechanical parameters characterizing the cellular state. Finally, experiments and dissipative particle dynamics demonstrate collective stiffness-based contact guidance. This work identifies stiffness heterogeneity as a fundamental regulator of cell and tissue organization and provides a framework for designing mechanoregulatory biomaterials.

biophysics↗

bioRxiv2024

Effect of the Environmental Mechanical Heterogeneity on T Cell Function

T cells, key players in the immune system, recognize antigens via T-cell receptors (TCRs) and require additional costimulatory and cytokine signals for full activation. Beyond biochemical signals, T cells also respond to mechanical cues such as tissue stiffness. Traditional ex-vivo mechanostimulating platforms, however, present a uniform mechanical environment, unlike the heterogeneous conditions T cells encounter in-vivo. This work introduces a novel mechanically heterogeneous environment, with alternating soft and stiff microdomains, to mimic the complex mechanical signals T cells face. Results show that T cells exposed to this heterogeneous environment do not average the mechanical signals but instead respond similarly to those on a homogeneously soft surface, leading to lower activation compared to those on a stiff surface. Interestingly, long-term exposure to these patterns enhances the proliferation of central memory and effector T cell phenotypes, similar to stiff environments. These findings reveal the non-linear nature of T cell mechanosensing and suggest that mechanical heterogeneity plays a critical role in modulating T cell responses, providing new insights into T cell activation and potential implications for immunotherapies.

immunology↗