Biology subjects

Segal, Y.

Publications and source records attributed to Segal, Y..

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

Deciphering the role of the nanoscale clustering of activating and costimulatory antibodies on T cell activation

In a joint experimental and a modeling effort, we explored the regulation of T cell activation and cytotoxicity by the nanoscale clustering and surface density of activating and costimulatory antibodies. Specifically, we simulated T cells on nanolithographically patterned arrays of clusters of these antibodies, systematically varying the cluster size from intermediate to large and overall antibody density. We found that T-cell activation correlated more with global antibody density than with cluster size, such that at low density arrays were inefficient in activation, while high density arrays saturated the signal. However, when T-cells were exposed to patterns of low global densities but small, very dense clusters, full activation of T cells was achieved. These results could be rationalized using the membrane-fluctuation-model that integrates the cooperative effects between bonds with mechanical feedback from the cell activation. This insight into the spatial organization of activating ligands provides an important understanding of the mechanism of T cell activation and allows for the design of more effective T cell activation platforms for immunotherapy.

immunology↗