Epidermal growth factor receptor (EGFR) interacts with integrins during cell spreading and motility, but little is known about the role of EGFR in these mechanosensing processes. Here we show, using two different cell lines, that in serum- and EGF-free conditions, EGFR or HER2 activity increase spreading and rigidity-sensing contractions on rigid, but not soft, substrates. Contractions peak after 15–20 min, but diminish by tenfold after 4 h. Addition of EGF at that point increases spreading and contractions, but this can be blocked by myosin-II inhibition. We further show that EGFR and HER2 are activated through phosphorylation by Src family kinases (SFK). On soft surfaces, neither EGFR inhibition nor EGF stimulation have any effect on cell motility. Thus, EGFR or HER2 can catalyse rigidity sensing after associating with nascent adhesions under rigidity-dependent tension downstream of SFK activity. This has broad implications for the roles of EGFR and HER2 in the absence of EGF both for normal and cancerous growth.

中文翻译：

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EGFR和HER2仅在刚性基质上激活刚性感应

表皮生长因子受体（EGFR）在细胞扩散和运动过程中与整合素相互作用，但对EGFR在这些机械传感过程中的作用了解甚少。在这里，我们显示了使用两种不同的细胞系，在无血清和无EGF的条件下，EGFR或HER2活性增加了在刚性而不是软性基质上的铺展和刚性敏感性收缩。收缩在15–20 分钟后达到峰值，但在4次后收缩减少十倍 H。在这一点上添加EGF会增加扩散和收缩，但是可以被肌球蛋白II抑制所阻断。我们进一步表明，EGFR和HER2通过Src家族激酶（SFK）的磷酸化而被激活。在柔软的表面上，EGFR抑制和EGF刺激均不会对细胞运动产生任何影响。因此，在SFK活性下游，在刚度依赖性的张力下，EGFR或HER2与新生的粘连相关联后，可以催化刚度传感。在不存在正常生长和癌生长的EGF的情况下，这对EGFR和HER2的作用具有广泛的意义。