an adhesion-dependent switch between mechanisms that determine motile cell shape一个adhesion-dependent之间切换机制,确定能动的细胞形状.pdfVIP

An Adhesion-Dependent Switch between Mechanisms That Determine Motile Cell Shape 1 2 3 2 1,4 Erin L. Barnhart , Kun-Chun Lee , Kinneret Keren , Alex Mogilner , Julie A. Theriot * 1 Department of Biochemistry and Howard Hughes Medical Institute, Stanford School of Medicine, Stanford, California, United States of America, 2 Department of Mathematics, University of California, Davis, California, United States of America, 3 Department of Physics and Russell Berrie Nanotechnology Institute, Technion – Israel Institute of Technology, Haifa, Israel, 4 Department of Microbiology and Immunology, Stanford School of Medicine, Stanford, California, United States of America Abstract Keratocytes are fast-moving cells in which adhesion dynamics are tightly coupled to the actin polymerization motor that drives migration, resulting in highly coordinated cell movement. We have found that modifying the adhesive properties of the underlying substrate has a dramatic effect on keratocyte morphology. Cells crawling at intermediate adhesion strengths resembled stereotypical keratocytes, characterized by a broad, fan-shaped lamellipodium, clearly defined leading and trailing edges, and persistent rates of protrusion and retraction. Cells at low adhesion strength were small and round with highly variable protrusion and retraction rates, and cells at high adhesion strength were large and asymmetrical and, strikingly, exhibited traveling waves of protrusion. To elucidate the mechanisms by which adhesion strength determines cell behavior, we examined the organization of adhesions, myosin II, and the actin network in keratocytes migrating on substrates with different adhesion strengths. On th