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The consequence of substrates of large-scale rigidity on actin network tension in adherent cells
Authors:Ian Manifacier  Kevin M Beussman  Sangyoon J Han  Nathan J Sniadecki  Imad About
Institution:1. Aix Marseille Univ, CNRS, ISM, Marseille, France;2. Aix Marseille University, APHM, CNRS, ISM, Sainte-Marguerite Hospital, Institute for Locomotion, Marseille, France;3. Department of Mechanical Engineering, University of Washington, Seattle, WA, USA;4. Center for Cardiovascular Biology, University of Washington, Seattle, WA, USA;5. Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA, USA;6. Department of Cell Biology, Harvard Medical School, Boston, WA, USA;7. Department of Cell Biology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX;8. Department of Bioengineering, University of Washington, Seattle, WA, USA
Abstract:Abstract

There is compelling evidence that substrate stiffness affects cell adhesion as well as cytoskeleton organization and contractile activity. This work was designed to study the cytoskeletal contractile activity of single cells plated on micropost substrates of different stiffness using a numerical model simulating the intracellular tension of individual cells. We allowed cells to adhere onto micropost substrates of various rigidities and used experimental traction force data to infer cell contractility using a numerical model. The model shows that higher substrate stiffness leads to an increase in intracellular tension. The strength of this model is its ability to calculate the mechanical state of each cell in accordance to its individual cytoskeletal structure. This is achieved by regenerating a numerical cytoskeleton based on microscope images of the actin network of each cell. The resulting numerical structure consequently represents pulling characteristics on its environment similar to those generated by the cell in-vivo. From actin imaging we can calculate and better understand how forces are transmitted throughout the cell.
Keywords:Actin  microscope image  focal adhesion  rigidity  cytoskeleton  in silico modeling  cross linear tension  stress fiber  divided medium mechanics
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