A minimal physical model for curvotaxis driven by curved protein complexes at the cell's leading edge

• 成果类型: Article
• 署名作者: Sadhu, Raj Kumar; Lucianob, Marine; Xi, Wang; Martinez-Torres, Cristina; Schroeder, Marcel; Blum, Christoph; Tarantola, Marco; Villa, Stefano; Penic, Samo; Iglic, Ales; Betae, Carsten; Steinbock, Oliver; Bodenschatz, Eberhard; Ladoux, Benoit; Gabriele, Sylvain; Gov, Nir S.
• 署名单位: Weizmann Institute of Science; University of Geneva; University of Mons; Centre National de la Recherche Scientifique (CNRS); Universite Paris Cite; University of Potsdam; Max Planck Society; University of Ljubljana; Kanazawa University; State University System of Florida; Florida State University; Centre National de la Recherche Scientifique (CNRS); CNRS - Institute of Chemistry (INC); Universite PSL; UNICANCER; Institut Curie; Sorbonne Universite
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-15185
• DOI: 10.1073/pnas.2306818121
• 发表日期: 2024-03-19
• 关键词: actin dynamics; migration; wasp

摘要

Cells often migrate on curved surfaces inside the body, such as curved tissues, blood vessels, or highly curved protrusions of other cells. Recent in vitro experiments provide clear evidence that motile cells are affected by the curvature of the substrate on which they migrate, preferring certain curvatures to others, termed curvotaxis. The origin and underlying mechanism that gives rise to this curvature sensitivity are not well understood. Here, we employ a minimal cell model which is composed of a vesicle that contains curved membrane protein complexes, that exert protrusive forces on the membrane (representing the pressure due to actin polymerization). This minimalcell model gives rise to spontaneous emergence of a motile phenotype, driven by a lamellipodia-like leading edge. By systematically screening the behavior of this model on different types of curved substrates (sinusoidal, cylinder, and tube), we show that minimal ingredients and energy terms capture the experimental data. The model recovers the observed migration on the sinusoidal substrate, where cells move along the grooves (minima), while avoiding motion along the ridges. In addition, the model predicts the tendency of cells to migrate circumferentially on convex substrates and axially on concave ones. Both of these predictions are verified experimentally, on several cell types. Altogether, our results identify the minimization of membrane -substrate adhesion energy and binding energy between the membrane protein complexes as key players of curvotaxis in cell migration.