Narasimhan Badri Narayanan, Fraley Stephanie I
Department of Bioengineering, University of California, San Diego, La Jolla, CA 92093, USA.
bioRxiv. 2024 Jul 29:2024.07.28.605514. doi: 10.1101/2024.07.28.605514.
In native extracellular matrices (ECM), cells can use matrix metalloproteinases (MMPs) to degrade and remodel their surroundings. Likewise, synthetic matrices have been engineered to facilitate MMP-mediated cleavage that enables cell spreading, migration, and interactions. However, the intersection of matrix degradability and mechanical properties has not been fully considered. We hypothesized that immediate mechanical changes result from the action of MMPs on the ECM and that these changes are sensed by cells. Using atomic force microscopy (AFM) to measure cell-scale mechanical properties, we find that both fibrillar collagen and synthetic degradable matrices exhibit enhanced stress relaxation after MMP exposure. Cells respond to these relaxation differences by altering their spreading and focal adhesions. We demonstrate that stress relaxation can be tuned through the rational design of matrix degradability. These findings establish a fundamental link between matrix degradability and stress relaxation, which may impact a range of biological applications.
在天然细胞外基质（ECM）中，细胞可以利用基质金属蛋白酶（MMPs）来降解和重塑其周围环境。同样，合成基质也经过设计，以促进MMP介导的裂解，从而实现细胞铺展、迁移和相互作用。然而，基质可降解性和机械性能之间的交叉尚未得到充分考虑。我们假设，MMPs对ECM的作用会导致即时的机械变化，并且这些变化会被细胞感知。通过使用原子力显微镜（AFM）测量细胞尺度的机械性能，我们发现，在MMP暴露后，纤维状胶原蛋白和合成可降解基质都表现出增强的应力松弛。细胞通过改变其铺展和粘着斑来应对这些松弛差异。我们证明，应力松弛可以通过合理设计基质可降解性来调节。这些发现建立了基质可降解性和应力松弛之间的基本联系，这可能会影响一系列生物学应用。
