MECHANICAL FORCES REGULATE FOCAL ADHESION AND COSTAMERE ASSEMBLY IN CARDIAC MYOCYTES

To determine whether the formation and maintenance of focal adhesions and costameres in cardiac myocytes are influenced by the mechanical fo rces that they transmit, we mechanically unloaded these cells by inhib iting their spontaneous contractile activity with the calcium-channel blocker nifedipine (12 mu M). Interference-reflection and fluorescence microscopy revealed that within 24 h of arrest, beta(1)-integrin- and vinculin-positive focal adhesions and costameres were disrupted. Loss of mature beta(1)-integrin from the cell surface was observed in cell surface-labeling experiments and in Western blots. Subjecting nonbeat ing cells to a 5% static stretch for 24 h resulted in an increase of 2 1% for beta(1)-integrin and 39% for vinculin. Stretching beating cells resulted in 71 and 9% increases, respectively. Intracellular concentr ations of pre-beta(1) were not affected by contractile activity or by stretch. Our results indicate that mechanical forces stabilize the cel lular levels of beta(1)-integrin and vinculin by possibly regulating t heir association with the formation and maintenance of focal adhesions and costameres.