Enhanced substrate stress relaxation promotes filopodia-mediated cell migration.

Enhanced substrate stress relaxation promotes filopodia-mediated cell migration.
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增强的底物应力松弛促进丝状伪足介导的细胞迁移。

DOI:
10.1038/s41563-021-00981-w
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发表时间:
2021-09
期刊:
影响因子:
41.2
通讯作者:
Chaudhuri O
Chaudhuri O
中科院分区:
材料科学1区
文献类型:
--
作者:
Adebowale K;Gong Z;Hou JC;Wisdom KM;Garbett D;Lee HP;Nam S;Meyer T;Odde DJ;Shenoy VB;Chaudhuri O

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细胞在2D基质上迁移的典型特征是前沿的片状脂膜、成熟的局灶性粘连和弥漫的形态。这些观察结果源于粘附性细胞在坚硬的弹性基质上的迁移研究,因为大多数细胞不会在柔软的弹性基质上迁移。然而,许多生物组织是柔软的和粘弹性的,随着时间的推移,随着时间的推移,对变形的反应会表现出应力松弛。在这里,我们系统地研究了衬底应力松弛对细胞在软衬底上迁移的影响。我们发现细胞在弹性模数为2kpa的衬底上迁移最少,或者表现出缓慢的应力松弛,但在2kpa的衬底上迁移得很强劲,表现出快速的应力松弛。值得注意的是,迁移细胞没有扩散,也没有延伸薄片状突起,而是呈圆形,丝状突起在前缘延伸,并显示出小的新生粘连。基于马达-离合器框架的细胞迁移计算模型预测了观察到的底物应力松弛对细胞迁移和丝状孢子动力学的影响。我们的发现确立了底物应力松弛是细胞在软底物上强劲迁移的关键要求,并揭示了以圆形形态、丝状足突和弱粘连为标志的2D细胞迁移模式。现在已经研究了底物应力松弛对细胞运动的影响。虽然细胞通常不会在软弹性基质上迁移,但现在的研究表明,细胞在软粘弹性基质上的迁移速度很快,应力松弛速度很快,迁移模式以圆形细胞形态和在前沿延伸的丝状足突为标志。
Cell migration on 2D substrates is typically characterized by lamellipodia at the leading edge, mature focal adhesions, and spread morphologies. These observations result from adherent cell migration studies on stiff, elastic substrates, as most cells do not migrate on soft, elastic substrates. However, many biological tissues are soft and viscoelastic, exhibiting stress relaxation over time in response to a deformation. Here, we systematically investigate the impact of substrate stress relaxation on cell migration on soft substrates. We find that cells migrate minimally on substrates with an elastic modulus of 2 kPa that are elastic or exhibit slow stress relaxation but migrate robustly on 2 kPa substrates that exhibit fast stress relaxation. Strikingly, migrating cells were not spread and did not extend lamellipodial protrusions, but were instead rounded, with filopodia protrusions extending at the leading edge, and exhibited small nascent adhesions. Computational models of cell migration based on a motor-clutch framework predict the observed impact of substrate stress relaxation on cell migration and filopodia dynamics. Our findings establish substrate stress relaxation as a key requirement for robust cell migration on soft substrates and uncover a mode of 2D cell migration marked by round morphologies, filopodia protrusions, and weak adhesions. The impact of substrate stress relaxation on cell motility has now been investigated. While cells do not typically migrate on soft elastic substrates, it is now shown that cells migrate robustly on soft viscoelastic substrates with fast stress relaxation using a migration mode marked by rounded cell morphologies and filopodia protrusions extending at the leading edge.
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发表时间: 1982-03
期刊: The Journal of cell biology
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