Physics Department, Syracuse University, Syracuse, New York 13244, United States.
BioInspired Institute, Syracuse University, Syracuse, New York 13244, United States.
ACS Appl Bio Mater. 2022 Feb 21;5(2):552-561. doi: 10.1021/acsabm.1c01046. Epub 2022 Jan 7.
The ability of cells to take and change shape is a fundamental feature underlying development, wound repair, and tissue maintenance. Central to this process is physical and signaling interactions between the three cytoskeletal polymeric networks: F-actin, microtubules, and intermediate filaments (IFs). Vimentin is an IF protein that is essential to the mechanical resilience of cells and regulates cross-talk among the cytoskeleton, but its role in how cells sense and respond to the surrounding extracellular matrix is largely unclear. To investigate vimentin's role in substrate sensing, we designed polyacrylamide hydrogels that mimic the elastic and viscoelastic nature of tissues. Using wild-type and vimentin-null mouse embryonic fibroblasts, we show that vimentin enhances cell spreading on viscoelastic substrates, even though it has little effect in the limit of purely elastic substrates. Our results provide compelling evidence that vimentin modulates how cells sense and respond to their environment and thus plays a key role in cell mechanosensing.
细胞的变形和迁移能力是发育、伤口修复和组织维持的基础。这个过程的核心是细胞内三个细胞骨架聚合网络:肌动蛋白丝、微管和中间丝(IFs)之间的物理和信号相互作用。波形蛋白是一种 IF 蛋白,对细胞的机械弹性至关重要,并调节细胞骨架之间的串扰,但它在细胞如何感知和响应周围细胞外基质方面的作用在很大程度上尚不清楚。为了研究波形蛋白在底物感知中的作用,我们设计了聚丙酰胺水凝胶,以模拟组织的弹性和粘弹性。使用野生型和波形蛋白缺失型的小鼠胚胎成纤维细胞,我们表明,波形蛋白增强了细胞在粘弹性底物上的铺展,尽管在纯弹性底物的极限情况下,它的影响很小。我们的结果提供了令人信服的证据,表明波形蛋白调节细胞如何感知和响应其环境,因此在细胞机械感知中发挥关键作用。