Single-cell and collective geometry sensing of biomaterial surfaces with micron-scale, smoothly curved topologies

P. Rougerie1, L. Pieuchot2, B. Pontes3, F. de Sá1, N. Sgambato1, M. Bigerelle4, N. Bessa Viana3, K.Anselme2, M. Farina de Souza1; 1Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil, 2Institutde Science des Materiaux de Mulhouse , Universite de Haute Alsace, Mulhouse , France, 3Instituto deFísica, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil, 4Departement de Mecanique,Universite de Valenciennes et du Hainaut Cambresis, Valenciennes, FranceCells not only interact with their environment through the well‐known chemosensing and mechanosensing but also through the perception of substrate topology. The notion that the local geometry is a also carrier of information for the cells has thus great consequences for regenerative medicine and tissue engineering. Nanometric topologies have already been shown to cause various effects on cell morphology and behavior mediated by spatial restrictions on focal adhesion formation. On the contrary, large micrometric features impose morphological constraints over the entire cell body and thus present a different challenge of topology reading by the cells. Many studies have investigated the cell response to micrometric topologies with sharp surface features (edges, angles). However, little is known about the effect of of large smoothly curved micrometric features presenting no edges or discontinuities. In particular, the effect of micrometric substrate curvatures on the collective behavior of epithelial colonies cannot be extrapolated from single cells because of the presence of intercellular mechanical tensions. Here we first show that isolated cells are able to sense large, cell‐scale smooth grooves by elongating and aligning with them. This is the first demonstration that the cellular toposensing does not necessitates the presence of angles, as purely smooth curved surfaces also guide cell deformation like sharp grooves and ridges do. Importantly, we report that dynamic, expanding epithelial colonies also elongate and grow along the topology main axis, while static mature epithelial monolayers show no signs of toposensing. This indicates that the sensitivity to micrometric smooth grooves is conserved through scales, from single cells to cohesive pluricellular tissues. It further suggests that toposensing is allowed by a certain state of cytoskeleton organization and dynamics progressively lost in the course of cell aggregation and epithelial maturation