A Molecular Clutch Model of Cellular Adhesion on Viscoelastic Substrate
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摘要: 细胞外基质由大量胶原蛋白和纤维蛋白组成,这些基质蛋白形成复杂的交联网络状结构,具有黏弹性力学特性.研究表明,黏弹性基质能显著影响细胞迁移、增殖和分化等生理行为,还能影响癌症转移和组织纤维化等疾病的发生与发展.然而,细胞感知细胞外基质黏弹性力学特性的分子机制仍不清楚.该文通过建立细胞黏附力学模型,从分子层次揭示细胞黏附在细胞响应外界黏弹性力学微环境中的作用.结果表明,细胞能通过调控细胞黏附动力学(包括黏附周期和黏附形成时间)响应细胞外基质的黏弹性力学特性.通过将模型计算结果与实验现象相比较,验证了模型的正确性.细胞黏附力学模型将为组织工程中细胞力学微环境的构建奠定理论基础.Abstract: The viscoelastic nature of the microenvironment of a cell is critical to cell mechanobiology, and modulates the mechanical feedback between cells and extracellular matrix. However, the mechanisms underlying the ways that cells actively sense and respond to a viscoelastic microenvironment remain elusive. We therefore developed a molecular clutch model of cell traction to predict the effects of substrate viscoelasticity on the dynamics of focal adhesions connecting the intracellular actin cytoskeleton to a viscoelastic substrate. The model predicts that certain levels of viscoelastic damping can increase cell tractions on relatively compliant substrates, and that this damping reduces cell tractions on relatively stiff substrates. The model predictions are qualitatively consistent well with reported experimental observations. The model offers physical insights into the role of substrate viscoelasticity on cell tractions and cell spreading.
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Key words:
- Viscoelasticity /
- mechanotransduction /
- cell adhesion /
- mechanical microenvironment
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