Lehrstuhl für Biophysik E27, Physics Department and Center for Protein Assemblies CPA, Technical University Munich (TUM), Garching, Germany.
Institute of Stem Cell Research, Helmholtz Center for Health and Environmental Research Munich, Neuherberg, Germany.
Nat Commun. 2021 May 12;12(1):2759. doi: 10.1038/s41467-021-22988-2.
Epithelial branch elongation is a central developmental process during branching morphogenesis in diverse organs. This fundamental growth process into large arborized epithelial networks is accompanied by structural reorganization of the surrounding extracellular matrix (ECM), well beyond its mechanical linear response regime. Here, we report that epithelial ductal elongation within human mammary organoid branches relies on the non-linear and plastic mechanical response of the surrounding collagen. Specifically, we demonstrate that collective back-and-forth motion of cells within the branches generates tension that is strong enough to induce a plastic reorganization of the surrounding collagen network which results in the formation of mechanically stable collagen cages. Such matrix encasing in turn directs further tension generation, branch outgrowth and plastic deformation of the matrix. The identified mechanical tension equilibrium sets a framework to understand how mechanical cues can direct ductal branch elongation.
上皮分支伸长是各种器官分支形态发生过程中的一个核心发育过程。这种进入大型分枝上皮网络的基本生长过程伴随着周围细胞外基质（ECM）的结构重组，远远超出了其机械线性响应范围。在这里，我们报告说，人类乳腺类器官分支内的导管伸长依赖于周围胶原的非线性和塑性力学响应。具体来说，我们证明了分支内细胞的集体来回运动产生的张力足以诱导周围胶原网络的塑性重组，从而形成机械稳定的胶原笼。这种基质包封反过来又指导进一步的张力产生、分支生长和基质的塑性变形。所确定的机械张力平衡为理解机械线索如何指导导管分支伸长提供了一个框架。
