CRITICAL CENTRIFUGAL FORCES INDUCE ADHESION RUPTURE OR STRUCTURAL REORGANIZATION IN CULTURED-CELLS

Cultured epithelial cells were exposed to accelerations ranging from 9 ,000 to 70,000g for time periods of 5, 15, or 60 min, by centrifugatio n in a direction tangential to their plastic substrate. Three regimes describe the cellular response: (1) Cell morphology and density remain unaltered at forces below a threshold of about 10(-7) N; (2) Between this critical force and a second threshold of about 1.5 10(-7) N, the number of adherent cells decreases exponentially with time and acceler ation, with no alteration of cell morphology. This behavior can be mod eled by a constant probability of detaching and by an exponential dist ribution of cell-to-substrate adhesive forces; (3) Past the second thr eshold, cells that are still adherent exhibit elongated morphologies, the degree of elongation increasing linearly with the force. The fact that cells lose their vinculin-rich focal contacts past the first thre shold and that cells cultured on gelatin-coated plastic show an increa sed resistance to detachment suggests a rupture of cell-to-substrate a dhesions upon centrifugation. Immunofluorescent labeling of cells for actin and tubulin shows a reorganization of the cytoskeleton upon cent rifugation, and treatment of cells with the drugs cytochalasin D and n ocodazole demonstrates that cytoskeletal elements are actively involve d in the structural deformation of cells past the second acceleration threshold, microtubules and microfilaments playing antagonistic roles. (C) 1996 Wiley-Liss, Inc.