Mechanical plasticity of collagen directs branch elongation in human mammary gland organoids.

Mechanical plasticity of collagen directs branch elongation in human mammary gland organoids.
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胶原蛋白的机械可塑性指导人类乳腺类器官的分支伸长。

DOI:
10.1038/s41467-021-22988-2
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发表时间:
2021-05-12
影响因子:
16.6
通讯作者:
Bausch AR
Bausch AR
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Buchmann B;Engelbrecht LK;Fernandez P;Hutterer FP;Raich MK;Scheel CH;Bausch AR

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上皮分支的伸长是不同器官分支形态发生过程中的一个重要发育过程。这个基本的生长过程,成为大型树枝状上皮网络伴随着周围的细胞外基质(ECM)的结构重组,远远超出其机械线性响应制度。在这里,我们报告说,上皮导管内的人类乳腺类器官分支的伸长依赖于周围的胶原蛋白的非线性和塑性机械响应。具体而言,我们证明了分支内细胞的集体来回运动产生足够强的张力,以诱导周围胶原蛋白网络的塑性重组,从而形成机械稳定的胶原蛋白笼。这种基质包裹反过来又引导基质的进一步张力产生、分支生长和塑性变形。所确定的机械张力平衡设置了一个框架,以了解机械线索如何引导导管分支伸长。来自单个原代人类细胞的乳腺类器官生长依赖于不同的形态发生过程。在这里,作者通过活细胞成像观察到细胞外基质的塑性机械反应和细胞迁移对于潜在的树枝状结构形成过程的重要性。
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. Mammary organoid growth from single primary human cells rely on distinct morphogenetic processes. Here, the authors observe by live cell imaging the importance of the plastic mechanical response of the extracellular matrix and cell migration for the underlying arborized structure formation process.
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