| Popis: |
In disease and development, cells sense and migrate across mechanically dissimilar environments. We investigated whether mechanical memory of past environments empowers cells to navigate new, three-dimensional environments. Here, we show that cells primed by stiff matrices apply higher forces, compared to soft-primed cells, to accumulate and align collagen fibers towards sustained invasion. This priming advantage persists in dense or stiffened collagen. Through an energy-minimization model, we elucidate how memory-laden cells overcome mechanosensing of softer or challenging environments via a cell-matrix transfer of memory. Consistent with model predictions, depletion of α-catenin and YAP hamper coordinated forces and cellular memory required for collagen remodeling before invasion. We release tension in collagen fibers via laser ablation and disable fiber remodeling by lysyl-oxidase inhibition; both of which disrupt cell-to-matrix transfer of memory and reduce invasion. These results have implications for cancer, fibrosis, and aging, where potential matrix memory may generate prolonged cellular response.One-Sentence SummaryCell invasion across mechanically dissimilar environments is mediated by force-based storage and extraction of cell and matrix memory. |
