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Elife ; 102021 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-34609280


During morphogenesis, epithelial sheets remodel into complex geometries. How cells dynamically organise their contact with neighbouring cells in these tightly packed tissues is poorly understood. We have used light-sheet microscopy of growing mouse embryonic lung explants, three-dimensional cell segmentation, and physical theory to unravel the principles behind 3D cell organisation in growing pseudostratified epithelia. We find that cells have highly irregular 3D shapes and exhibit numerous neighbour intercalations along the apical-basal axis as well as over time. Despite the fluidic nature, the cell packing configurations follow fundamental relationships previously described for apical epithelial layers, that is, Euler's polyhedron formula, Lewis' law, and Aboav-Weaire's law, at all times and across the entire tissue thickness. This arrangement minimises the lateral cell-cell surface energy for a given cross-sectional area variability, generated primarily by the distribution and movement of nuclei. We conclude that the complex 3D cell organisation in growing epithelia emerges from simple physical principles.

Pulmão/embriologia , Animais , Células Epiteliais/citologia , Epitélio/embriologia , Camundongos , Morfogênese
Development ; 148(9)2021 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-33946098


During lung development, epithelial branches expand preferentially in a longitudinal direction. This bias in outgrowth has been linked to a bias in cell shape and in the cell division plane. How this bias arises is unknown. Here, we show that biased epithelial outgrowth occurs independent of the surrounding mesenchyme, of preferential turnover of the extracellular matrix at the bud tips and of FGF signalling. There is also no evidence for actin-rich filopodia at the bud tips. Rather, we find epithelial tubes to be collapsed during early lung and kidney development, and we observe fluid flow in the narrow tubes. By simulating the measured fluid flow inside segmented narrow epithelial tubes, we show that the shear stress levels on the apical surface are sufficient to explain the reported bias in cell shape and outgrowth. We use a cell-based vertex model to confirm that apical shear forces, unlike constricting forces, can give rise to both the observed bias in cell shapes and tube elongation. We conclude that shear stress may be a more general driver of biased tube elongation beyond its established role in angiogenesis. This article has an associated 'The people behind the papers' interview.

Fenômenos Biomecânicos , Rim/crescimento & desenvolvimento , Pulmão/crescimento & desenvolvimento , Organogênese , Animais , Biofísica , Forma Celular , Células Epiteliais/citologia , Matriz Extracelular , Feminino , Masculino , Mesoderma/metabolismo , Camundongos , Modelos Biológicos , Morfogênese , Pseudópodes
Phys Rev Lett ; 123(5): 058002, 2019 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-31491319


We report on the buckling and subsequent collapse of orthotropic elastic spherical shells under volume and pressure control. Going far beyond what is known for isotropic shells, a rich morphological phase space with three distinct regimes emerges upon variation of shell slenderness and degree of orthotropy. Our extensive numerical simulations are in agreement with experiments using fabricated polymer shells. The shell buckling pathways and corresponding strain energy evolution are shown to depend strongly on material orthotropy. We find surprisingly robust orthotropic structures with strong similarities to stomatocytes and tricolpate pollen grains, suggesting that the shape of several of Nature's collapsed shells could be understood from the viewpoint of material orthotropy.

Nat Commun ; 10(1): 2285, 2019 05 23.
Artigo em Inglês | MEDLINE | ID: mdl-31123251


Growing tissue and bacterial colonies are active matter systems where cell divisions and cellular motion generate active stress. Although they operate in the non-equilibrium regime, these biological systems can form large-scale ordered structures. How mechanical instabilities drive the dynamics of active matter systems and form ordered structures are not well understood. Here, we use chaining Bacillus subtilis, also known as a biofilm, to study the relation between mechanical instabilities and nematic ordering. We find that bacterial biofilms have intrinsic length scales above which a series of mechanical instabilities occur. Localized stress and friction drive buckling and edge instabilities which further create nematically aligned structures and topological defects. We also observe that topological defects control stress distribution and initiate the formation of sporulation sites by creating three-dimensional structures. In this study we propose an alternative active matter platform to study the essential roles of mechanics in growing biological tissue.

Bacillus subtilis/fisiologia , Biofilmes , Microscopia Intravital/métodos , Bacillus subtilis/ultraestrutura , Fenômenos Biomecânicos , Microscopia Eletrônica de Varredura/métodos , Microscopia de Fluorescência/métodos , Estresse Mecânico , Imagem com Lapso de Tempo/métodos