Mechanics of cell spreading: role of myosin II.
As it migrates over a substratum, a cell must exert different kinds of forces that act at various cellular locations and at specific times. These forces must therefore be coordinately regulated. The Rho-family GTPases Rac1 and Cdc42 promote actin polymerization that drives extension of the leading cell edge. Subsequently, RhoA regulates myosin-dependent contractile force, which is required for formation of adhesive contacts and stress fibers. During cell spreading, however, the activity of RhoA is reduced by a mechanism involving the tyrosine kinases c-Src and focal adhesion kinase (FAK), and the p190RhoGAP. It has been proposed that this reduction of RhoA activity facilitates edge extension by reducing myosin-dependent contractile forces that could resist this process. We have directly tested this hypothesis by correlating myosin activity with the rate of cell spreading on a substratum. The rate of spreading is inversely related to the myosin activity. Furthermore, spreading is inhibited by low concentrations of cytochalasin D, as expected for a process that depends on the growth of uncapped actin filaments. Cell indentation measurements show that a myosin-dependent viscoelastic force resists cell deformation.
Wakatsuki
Tetsuro
T
Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St Louis, MO 63110, USA.
Wysolmerski
Robert B
RB
Elson
Elliot L
EL
D000818:Animals; D002227:Carbazoles / Q000494:pharmacology; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D048429:Cell Size / Q000187:drug effects / Q000502:physiology; D002642:Chick Embryo; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D015638:Cytochalasin D / Q000494:pharmacology; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D007211:Indoles / Q000494:pharmacology; D018994:Myosin Light Chains / Q000378:metabolism; D024462:Myosin Type II / Q000502:physiology*; D010766:Phosphorylation / Q000187:drug effects; D019311:Staurosporine / Q000494:pharmacology; D013997:Time Factors
D002227:Carbazoles; D016895:Culture Media, Serum-Free; D007211:Indoles; D018994:Myosin Light Chains; C063769:KT 5926; D015638:Cytochalasin D; D024462:Myosin Type II; D019311:Staurosporine