title: Extracellular matrix scaffolding guides lumen elongation by inducing anisotropic intercellular mechanical tension.
abstract: The de novo formation of secretory lumens plays an important role during organogenesis. It involves the establishment of a cellular apical pole and the elongation of luminal cavities. The molecular parameters controlling cell polarization have been heavily scrutinized. In particular, signalling from the extracellular matrix (ECM) proved essential to the proper localization of the apical pole by directed protein transport. 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.
authors.affiliation: Mechanobiology Institute, National University of Singapore, Singapore 117411, Singapore.
authors.forename: Qiushi
authors.initials: Q
authors.lastname: Li
authors.affiliation: Mechanobiology Institute, National University of Singapore, Singapore 117411, Singapore.
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Biological Sciences, National University of Singapore, Singapore 117411, Singapore.
authors.forename: Perrine
authors.initials: P
authors.lastname: Pluchon
authors.affiliation: Mechanobiology Institute, National University of Singapore, Singapore 117411, Singapore.
authors.forename: Jeffrey
authors.identifier: http://orcid.org/0000-0003-2344-0036
authors.initials: J
authors.lastname: Robens
authors.affiliation: Institute of Molecular Cell Biology, A∗STAR, 61 Biopolis Drive, Singapore 138673, Singapore.
authors.forename: Keira
authors.initials: K
authors.lastname: Herr
authors.affiliation: Laboratoire d'Ingénierie des Systèmes Biologiques et des Procédés, Université de Toulouse, INSA, INRA, CNRS, 31077 Toulouse, France.
authors.forename: Myriam
authors.initials: M
authors.lastname: Mercade
authors.affiliation: Institute of Molecular Cell Biology, A∗STAR, 61 Biopolis Drive, Singapore 138673, Singapore.
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Thiery
authors.affiliation: Mechanobiology Institute, National University of Singapore, Singapore 117411, Singapore.|Department of Physiology, Yong Loo Lin School of Medicine, National University Health System, Singapore 117597, Singapore.|Institute of Bioengineering and Nanotechnology (IBN), Agency for Science, Technology and Research, Singapore 138669, Singapore.
authors.forename: Hanry
authors.identifier: http://orcid.org/0000-0002-0339-3685
authors.initials: H
authors.lastname: Yu
authors.affiliation: Mechanobiology Institute, National University of Singapore, Singapore 117411, Singapore.|Department of Biological Sciences, National University of Singapore, Singapore 117411, Singapore.|Institute of Molecular Cell Biology, A∗STAR, 61 Biopolis Drive, Singapore 138673, Singapore.|CNRS UMI3639, Singapore 117411, Singapore.
authors.forename: Virgile
authors.identifier: http://orcid.org/0000-0003-3949-2244
authors.initials: V
authors.lastname: Viasnoff
mesh_terms: D000818:Animals; D002448:Cell Adhesion / Q000502:physiology*; D002469:Cell Separation / Q000379:methods; D002478:Cells, Cultured; D005109:Extracellular Matrix / Q000378:metabolism*; D055785:Gene Knockdown Techniques / Q000379:methods; D016023:Integrins / Q000378:metabolism*; D008297:Male; D038081:Organogenesis / Q000502:physiology*; D017208:Rats, Wistar; D013314:Stress, Mechanical
chemical_list: D016023:Integrins