Extracellular matrix scaffolding guides lumen elongation by inducing anisotropic intercellular mechanical tension

Available online: https://www.nature.com/articles/ncb3310 

Abstract

The de novo formation of secretory lumens plays an important role during organogenesis. It involves the establishment of a cellular apical pole1 and the elongation of luminal cavities2. The molecular parameters controlling cell polarization have been heavily scrutinized3,4,5. In particular, signalling from the extracellular matrix (ECM) proved essential to the proper localization of the apical pole by directed protein transport6. However, little is known about the regulation of the shape and the directional development of lumen into tubes. We demonstrate that the spatial scaffolding of cells by ECM can control tube shapes and can direct their elongation. We developed a minimal organ approach comprising of hepatocyte doublets cultured in artificial microniches to precisely control the spatial organization of cellular adhesions in three dimensions. This approach revealed a mechanism by which the spatial repartition of integrin-based adhesion can elicit an anisotropic intercellular mechanical stress guiding the osmotically driven elongation of lumens in the direction of minimal tension. This mechanical guidance accounts for the different morphologies of lumen in various microenvironmental conditions.

Qiushi Li, Yue Zhang, Perrine Pluchon, Jeffrey Robens, Keira Herr, Myriam Mercade, Jean-Paul Thiery, Hanry Yu, and Virgile Viasnoff.

Nature Cell Biology 18, 311–318 (2016) doi:10.1038/ncb3310

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