학술논문

A minimal physical model for curvotaxis driven by curved protein complexes at the cell's leading edge.
Document Type
Article
Source
Proceedings of the National Academy of Sciences of the United States of America. 3/19/2024, Vol. 121 Issue 12, p1-12. 29p.
Subject
*MEMBRANE proteins
*CURVED surfaces
*BINDING energy
*CELL migration
*BLOOD vessels
*LABOR mobility
*PERMEATION tubes
Language
ISSN
0027-8424
Abstract
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. [ABSTRACT FROM AUTHOR]