20.500.12556/RUL-173643 A minimal physical model for curvotaxis driven by curved protein complexes at the cells leading edge 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 minimal-cell 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. cell motility curved proteins computer simulations Monte Carlo method mobilnost celice ukrivljeni proteini računalniške simulacije metoda Monte Carlo true false true Angleški jezik Slovenski jezik Članek v reviji 2025-09-19 10:04:53 2025-09-19 10:04:55 2025-11-11 03:56:07 0000-00-00 00:00:00 2024 0 0 Str. 1-12 no. 12, [article no.] e2306818121 Vol. 121 19. Mar. 2024 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 577 1091-6490 10.1073/pnas.2306818121 191263747 sadhu-et-al-2024-a-minimal-physical-model-for-curvotaxis-driven-by-curved-protein-complexes-at-the-cell-s-leading-edge.pdf sadhu-et-al-2024-a-minimal-physical-model-for-curvotaxis-driven-by-curved-protein-complexes-at-the-cell-s-leading-edge.pdf 1 B2391919E220B525ECD67C51E2F20B14 d71fcb2600c7d6b28975f9e7c25914d0e1e0967c9d8b90b32a117056c71c0a94 6c063534-952f-11f0-9328-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=218257 https://www.pnas.org/doi/10.1073/pnas.2306818121 1 2782f566-952f-11f0-9328-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=218256 Fakulteta za elektrotehniko 0 0 0