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It is well known that cells generate forces on 2D substrates. These forces increase with time till they reach a steady value. The magnitude of the steady force depends on the stiffness of the substrates. This force is beieved to serve as a cue for the cell resulting in a wide variety of cell functions. Here we show, using fibroblasts and high-speed, high-resolution florescent microscopy, that cell forces are dynamic at any state of the cell. Cells generate time varying contractile forces all around the periphery at discrete adhesion points. The forces typically increase with time, drop suddenly over a few millisecond time, and continue to increase again. The direction of the force and the rate of increase remain the same before and after the force drop. The force release at discrete adhesion points do not cause any change in forcing at nearby adhesion sites, implying that these time varying forces are localized. Cells may use such dynamic forcing mechanism to continuously probe the local microenvironment, and consequently sense stiffness gradients. A simple mathematical model, based on acto-myosin machinery, is developed to interpret the dynamic cell forces. |
