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Self-generated gradients steer collective migration on viscoelastic collagen networks
Nature Materials ( IF 41.2 ) Pub Date : 2022-05-30 , DOI: 10.1038/s41563-022-01259-5
Andrew G Clark 1, 2, 3 , Ananyo Maitra 4, 5 , Cécile Jacques 1 , Martin Bergert 6 , Carlos Pérez-González 1 , Anthony Simon 1 , Luc Lederer 1 , Alba Diz-Muñoz 6 , Xavier Trepat 7, 8, 9, 10 , Raphaël Voituriez 5, 11 , Danijela Matic Vignjevic 1
Affiliation  

Growing evidence suggests that the physical properties of the cellular microenvironment influence cell migration. However, it is not currently understood how active physical remodelling by cells affects migration dynamics. Here we report that cell clusters seeded on deformable collagen-I networks display persistent collective migration despite not showing any apparent intrinsic polarity. Clusters generate transient gradients in collagen density and alignment due to viscoelastic relaxation of the collagen networks. Combining theory and experiments, we show that crosslinking collagen networks or reducing cell cluster size results in reduced network deformation, shorter viscoelastic relaxation time and smaller gradients, leading to lower migration persistence. Traction force and Brillouin microscopy reveal asymmetries in force distributions and collagen stiffness during migration, providing evidence of mechanical cross-talk between cells and their substrate during migration. This physical model provides a mechanism for self-generated directional migration on viscoelastic substrates in the absence of internal biochemical polarity cues.



中文翻译:

自生梯度引导粘弹性胶原网络上的集体迁移

越来越多的证据表明,细胞微环境的物理特性会影响细胞迁移。然而,目前尚不清楚细胞的主动物理重塑如何影响迁移动力学。在这里,我们报告播种在可变形胶原蛋白-I 网络上的细胞簇显示出持续的集体迁移,尽管没有显示出任何明显的内在极性。由于胶原蛋白网络的粘弹性松弛,簇在胶原蛋白密度和排列中产生瞬态梯度。结合理论和实验,我们表明交联胶原蛋白网络或减小细胞簇大小会导致网络变形减少、粘弹性弛豫时间缩短和梯度变小,从而导致迁移持久性降低。牵引力和布里渊显微镜揭示了迁移过程中力分布和胶原刚度的不对称性,为迁移过程中细胞与其基质之间的机械串扰提供了证据。这种物理模型提供了一种在没有内部生化极性线索的情况下在粘弹性基质上自生成定向迁移的机制。

更新日期:2022-05-31
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