黏附强度和收缩性使转移性细胞具有趋触性。
Adhesion strength and contractility enable metastatic cells to become adurotactic.
机构信息
Department of Bioengineering, University of California, San Diego, La Jolla, CA 92093, USA; Department of Mechanical Engineering, San Diego State University, San Diego, CA 92182, USA.
Department of Bioengineering, University of California, San Diego, La Jolla, CA 92093, USA.
出版信息
Cell Rep. 2021 Mar 9;34(10):108816. doi: 10.1016/j.celrep.2021.108816.
Significant changes in cell stiffness, contractility, and adhesion, i.e., mechanotype, are observed during a variety of biological processes. Whether cell mechanics merely change as a side effect of or driver for biological processes is still unclear. Here, we sort genotypically similar metastatic cancer cells into strongly adherent (SA) versus weakly adherent (WA) phenotypes to study how contractility and adhesion differences alter the ability of cells to sense and respond to gradients in material stiffness. We observe that SA cells migrate up a stiffness gradient, or durotax, while WA cells largely ignore the gradient, i.e., adurotax. Biophysical modeling and experimental validation suggest that differences in cell migration and durotaxis between weakly and strongly adherent cells are driven by differences in intra-cellular actomyosin activity. These results provide a direct relationship between cell phenotype and durotaxis and suggest how, unlike other senescent cells, metastatic cancer cells navigate against stiffness gradients.
在各种生物学过程中，细胞的刚性、收缩性和粘附性（即力学特性）发生显著变化。细胞力学是否仅仅是生物过程的副作用或驱动力仍不清楚。在这里，我们将基因型相似的转移性癌细胞分为强粘附（SA）和弱粘附（WA）表型，以研究收缩性和粘附性差异如何改变细胞感知和响应材料刚度梯度的能力。我们观察到 SA 细胞在刚度梯度（即趋硬）上迁移，而 WA 细胞在很大程度上忽略了梯度（即趋软）。生物物理建模和实验验证表明，弱粘附和强粘附细胞之间在细胞迁移和趋硬行为上的差异是由细胞内肌动球蛋白活性的差异驱动的。这些结果提供了细胞表型和趋硬行为之间的直接关系，并表明转移性癌细胞如何不同于其他衰老细胞，在对抗刚度梯度时进行导航。
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