Charbonier Frank, Zhu Junqin, Slyman Raleigh, Allan Cole, Chaudhuri Ovijit
Department of Mechanical Engineering, Stanford University, Stanford, CA 94305.
Department of Biology, Stanford University, Stanford, CA 94305.
Proc Natl Acad Sci U S A. 2025 Apr 15;122(15):e2417290122. doi: 10.1073/pnas.2417290122. Epub 2025 Apr 9.
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.
上皮组织的集体迁移是发育形态发生和组织稳态的一个关键特征。细胞集体的连贯运动需要大规模的运动协调和力的产生，并且受到下层基质机械特性的影响。虽然组织粘弹性是生物组织普遍存在的特征，但其在介导集体细胞迁移中的作用尚不清楚。在这里，我们研究了基质应力松弛对微图案化上皮单层迁移的影响。相对于具有更快应力松弛（表现出更多粘性损失）的基质，上皮单层在具有较慢松弛时间尺度（更具弹性）的粘弹性藻酸盐基质上表现出更快的集体迁移。在缓慢松弛基质上更快的迁移与基质变形减少、单层流动性增加以及前导细胞形成增强有关。相比之下，在快速松弛基质上的单层会产生大量基质变形，并且在整体中更易受阻，单层边缘之外的瞬时片状伪足突起形成减少，导致整体扩张较慢。这项工作揭示了软质粘弹性材料上集体上皮动力学的特征，并增进了我们对组织尺度上细胞 - 基质相互作用的理解。
