Stabilizing to disruptive transition of focal adhesion response to mechanical forces |
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| Authors: | Dong Kong Baohua Ji Lanhong Dai |
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| Institution: | 1. State Key Laboratory of Nonlinear Mechanics (LNM), Institute of Mechanics, Chinese Academy of Sciences, Beijing 100190, China;2. Institute of Biomechanics and Biomedical Engineering, Department of Engineering Mechanics, Tsinghua University, Beijing 100084, China;1. Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, MO 63110, United States;2. Department of Mechanical Engineering and Materials Science, Washington University, St. Louis, MO 63130, United States;2. Department of Biomedical Engineering, University of Minnesota, Minneapolis, Minnesota;3. Brain Tumor and Neuro-Oncology Center, Cleveland Clinic, Cleveland, Ohio;2. Department of Applied Physics, Eindhoven University of Technology, Eindhoven, The Netherlands;3. Institute for Complex Molecular Systems, Eindhoven University of Technology, Eindhoven, The Netherlands;1. Department of Biological Sciences, Columbia University, New York, New York;2. Mechanobiology Institute, National University of Singapore, Singapore;1. Cell Biology and Physiology Center, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA;2. Institute for Theoretical Physics, University of Stuttgart, 70550 Stuttgart, Germany;1. Department of Biomedical Engineering, Virginia Commonwealth University, Richmond, Virginia |
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| Abstract: | Strong mechanical forces can, obviously, disrupt cell–cell and cell–matrix adhesions, e.g., cyclic uniaxial stretch induces instability of cell adhesion, which then causes the reorientation of cells away from the stretching direction. However, recent experiments also demonstrated the existence of force dependent adhesion growth (rather than dissociation). To provide a quantitative explanation for the two seemingly contradictory phenomena, a microscopic model that includes both integrin–integrin interaction and integrin–ligand interaction is developed at molecular level by treating the focal adhesion as an adhesion cluster. The integrin clustering dynamics and integrin–ligand binding dynamics are then simulated within one unified theoretical frame with Monte Carlo simulation. We find that the focal adhesion will grow when the traction force is higher than a relative small threshold value, and the growth is dominated by the reduction of local chemical potential energy by the traction force. In contrast, the focal adhesion will rupture when the traction force exceeds a second threshold value, and the rupture is dominated by the breaking of integrin–ligand bonds. Consistent with the experiments, these results suggest a force map for various responses of cell adhesion to different scales of mechanical force. |
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