Directional Cell Migration Guided by a Strain Gradient.
Directional Cell Migration Guided by a Strain Gradient.
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由应变梯度引导的定向细胞迁移。
DOI：
10.1002/smll.202302404
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发表时间：
2024
期刊：
影响因子：
--
通讯作者：
Sun,Yubing
中科院分区：
文献类型：
--
作者：
Yang,Feiyu;Chen,Pengcheng;Jiang,Han;Xie,Tianfa;Shao,Yue;Kim,Deok-Ho;Li,Bo;Sun,Yubing
应变梯度广泛存在于发育和生理活动中。细胞的定向运动对于适当的细胞定位是必不可少的，细胞定向迁移对细胞外基质的化学成分、刚性、密度和地形的梯度的响应已经得到了很好的证实。然而，目前尚不清楚施加在细胞上的应变梯度是否足以驱动细胞的定向迁移。在这项工作中，开发了一种可编程的单轴细胞拉伸装置，该装置可以在不改变衬底硬度或配体分布的情况下产生可控的应变梯度。结果表明，在≈为4%/mm应变梯度的静态拉伸和0.1HZ循环拉伸条件下，超过60%的单个大鼠胚胎成纤维细胞向低应变方向迁移。研究证实，这种反应不同于趋杜性反应或趋触性反应。焦点黏附分析证实，细胞低应变侧的接触面积和突起形成率较高。建立了一个二维扩展的电机-离合器模型，以证明应变引入的牵引力决定了整合素纤维连接蛋白对的捕捉-释放动力学，从而驱动了这种定向迁移。总之，这些结果建立了应变梯度作为调节细胞定向迁移的新线索，并可能为发育和组织修复提供新的见解。
Strain gradients widely exist in development and physiological activities. The directional movement of cells is essential for proper cell localization, and directional cell migration in responses to gradients of chemicals, rigidity, density, and topography of extracellular matrices have been well‐established. However; it is unclear whether strain gradients imposed on cells are sufficient to drive directional cell migration. In this work, a programmable uniaxial cell stretch device is developed that creates controllable strain gradients without changing substrate stiffness or ligand distributions. It is demonstrated that over 60% of the single rat embryonic fibroblasts migrate toward the lower strain side in static and the 0.1 Hz cyclic stretch conditions at ≈4% per mm strain gradients. It is confirmed that such responses are distinct from durotaxis or haptotaxis. Focal adhesion analysis confirms higher rates of contact area and protrusion formation on the lower strain side of the cell. A 2D extended motor‐clutch model is developed to demonstrate that the strain‐introduced traction force determines integrin fibronectin pairs' catch‐release dynamics, which drives such directional migration. Together, these results establish strain gradient as a novel cue to regulate directional cell migration and may provide new insights in development and tissue repairs.