journal article·2025-06Open access

Tension anisotropy drives fibroblast phenotypic transition by self-reinforcing cell–extracellular matrix mechanical feedback

Farid Alisafaei, Delaram Shakiba, Yuan Hong, Ghiska Ramahdita, Yuxuan Huang, Leanne E. Iannucci, Matthew D. Davidson, Mohammad Jafari, Jin Qian, Chengqing Qu, David Ju, Dashiell R. Flory, Yin-Yuan Huang, Prashant Gupta, Shumeng Jiang, Aliza Mujahid, Srikanth Singamaneni, Kenneth M. Pryse, Pen-hsiu Grace Chao, Jason A. Burdick, Spencer P. Lake, Elliot L. Elson, Nathaniel Huebsch, Vivek B. Shenoy, Guy M. Genin

Nature Materials· Volume 24· Issue 6

Abstract

Mechanical factors such as stress in the extracellular environment affect the phenotypic commitment of cells. Stress fields experienced by cells in tissues are multiaxial, but how cells integrate such information is largely unknown. Here we report that the anisotropy of stress fields is a critical factor triggering a phenotypic transition in fibroblast cells, outweighing the role of stress amplitude, a factor previously described to modulate such a transition. Combining experimental and computational approaches, we identified a self-reinforcing mechanism in which cellular protrusions interact with collagen fibres to establish tension anisotropy. This anisotropy, in turn, stabilizes the protrusions and enhances their contractile forces. Disruption of this self-reinforcing process, either by reducing tension anisotropy or by inhibiting contractile protrusions, prevents the phenotypic conversion of fibroblasts to contractile myofibroblasts. Overall, our findings support stress anisotropy as a factor modulating cellular responses, expanding our understanding of the role of mechanical forces in biological processes.
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Research context

OpenAlex topics: Cellular Mechanics and Interactions · 3D Printing in Biomedical Research · Spaceflight effects on biology

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