Extracellular matrix scaffolding guides lumen elongation by inducing anisotropic intercellular mechanical tension
2016
Li, Qiushi | Zhang, Yue | Pluchon, Perrine | Robens, Jeffrey | Herr, Keira | Mercade, Myriam | Thiery, Jean-Paul | Yu, Hanry | Viasnoff, Virgile | Mechanobiology Institute ; National University of Singapore (NUS) | Department of Biological Sciences ; Dartmouth College [Hanover] | Institute of Molecular Cell Biology ; Agency for science, technology and research [Singapore] (A*STAR) | Laboratoire d'Ingénierie des Systèmes Biologiques et des Procédés (LISBP) ; Institut National de la Recherche Agronomique (INRA)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse) ; Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS) | Université de Toulouse (UT) | Department of Physiology, Yong Loo Lin School of Medicine ; National University of Singapore (NUS) | Agency for science, technology and research [Singapore] (A*STAR) | Biomechanics of cellular contacts (BMC2) ; National University of Singapore (NUS)-Centre National de la Recherche Scientifique (CNRS) | MBI; IBN; NRF [CRP 001-084]; ANR | ANR-14-CE11-0019,soSPIM,Méthode de sectionnement optique pour la nanoscopie 3D par localisation de molécules individuelles pour l'étude des processus morphologiques(2014)
The de novo formation of secretory lumens plays an important role during organogenesis. It involves the establishment of a cellular apical pole(1) and the elongation of luminal cavities(2). The molecular parameters controlling cell polarization have been heavily scrutinized(3-5). In particular, signalling from the extracellular matrix (ECM) proved essential to the proper localization of the apical pole by directed protein transport(6). 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.
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