Collective migration of epithelial tissues is a critical feature of developmental morphogenesis and tissue homeostasis. Coherent motion of cell collectives requires large-scale coordination of motion and force generation and is influenced by mechanical properties of the underlying substrate. While tissue viscoelasticity is a ubiquitous feature of biological tissues, its role in mediating collective cell migration is unclear. Here, we have investigated the impact of substrate stress relaxation on the migration of micropatterned epithelial monolayers. Epithelial monolayers exhibit faster collective migration on viscoelastic alginate substrates with slower relaxation timescales, which are more elastic, relative to substrates with faster stress relaxation, which exhibit more viscous loss. Faster migration on slow-relaxing substrates is associated with reduced substrate deformation, greater monolayer fluidity, and enhanced leader cell formation. In contrast, monolayers on fast-relaxing substrates generate substantial substrate deformations and are more jammed within the bulk, with reduced formation of transient lamellipodial protrusions past the monolayer edge leading to slower overall expansion. This work reveals features of collective epithelial dynamics on soft, viscoelastic materials and adds to our understanding of cell–substrate interactions at the tissue scale.

中文翻译：

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底物应力松弛调节集体迁移上皮细胞的单层流动性和前导细胞形成


上皮组织的集体迁移是发育形态发生和组织稳态的关键特征。细胞集体的相干运动需要运动和力产生的大规模协调，并受底层基质的机械特性的影响。虽然组织粘弹性是生物组织中普遍存在的特征，但它在介导集体细胞迁移中的作用尚不清楚。在这里，我们研究了底物应力松弛对微图案上皮单层迁移的影响。上皮单层在粘弹性藻酸盐基质上表现出更快的集体迁移，弛豫时间尺度较慢，相对于应力松弛较快的基质，其弹性更大，表现出更多的粘性损失。在缓慢松弛的衬底上更快的迁移与衬底变形减少、单层流动性更大和领导细胞形成增强有关。相比之下，快速松弛衬底上的单层会产生大量的衬底变形，并且在块体内更加卡住，通过单层边缘的瞬态层状突起的形成减少，导致整体膨胀变慢。这项工作揭示了柔软、粘弹性材料上的集体上皮动力学特征，并增加了我们对组织尺度上细胞-基质相互作用的理解。