Curvotaxis directs cell migration through cell-scale curvature landscapes

Laurent Pieuchot (1, 2) , Julie Marteau (3) , Alain Guignandon (4) , Thomas dos Santos (1, 2) , Isabelle Brigaud (1, 2) , Pierre-Francois Chauvy (5) , Thomas Cloatre (1, 2) , Arnaud Ponche (1, 2) , Tatiana Petithory (1, 2) , Pablo Rougerie (6) , Maxime Vassaux (7) , Jean-Louis Milan (7) , Nayana Tusamda Wakhloo (1, 2) , Arnaud Spangenberg (1, 2) , Maxence Bigerelle (3, 8) , Karine Anselme (1, 2)

1 IS2M - Institut de Science des Matériaux de Mulhouse
2 UNISTRA - Université de Strasbourg
3 LAMIH - Laboratoire d'Automatique, de Mécanique et d'Informatique industrielles et Humaines - UMR 8201
4 SAINBIOSE - Santé Ingénierie Biologie Saint-Etienne
5 Micropat SA
6 Federal University of Rio de Janeiro
7 ISM - Institut des Sciences du Mouvement Etienne Jules Marey
8 INSA Hauts-De-France - INSA Institut National des Sciences Appliquées Hauts-de-France

Cells have evolved multiple mechanisms to apprehend and adapt finely to their environment. Here we report a new cellular ability, which we term ``curvotaxis'' that enables the cells to respond to cell-scale curvature variations, a ubiquitous trait of cellular biotopes. We develop ultra-smooth sinusoidal surfaces presenting modulations of curvature in all directions, and monitor cell behavior on these topographic landscapes. We show that adherent cells avoid convex regions during their migration and position themselves in concave valleys. Live imaging combined with functional analysis shows that curvotaxis relies on a dynamic interplay between the nucleus and the cytoskeleton-the nucleus acting as a mechanical sensor that leads the migrating cell toward concave curvatures. Further analyses show that substratum curvature affects focal adhesions organization and dynamics, nuclear shape, and gene expression. Altogether, this work identifies curvotaxis as a new cellular guiding mechanism and promotes cell-scale curvature as an essential physical cue.

Mots clés: Biomaterials; Cell migration

Domaines: Sciences du Vivant [q-bio]; Matériaux; Biologie cellulaire

Laurent Pieuchot, Julie Marteau, Alain Guignandon, Thomas dos Santos, Isabelle Brigaud, et al.. Curvotaxis directs cell migration through cell-scale curvature landscapes. Nature Communications, 2018, 9, ⟨10.1038/s41467-018-06494-6⟩. ⟨hal-01960533⟩