3.8 Article

Structural Modeling of Mechanosensitivity in Non-Muscle Cells: Multiscale Approach to Understand Cell Sensing

Journal

ACS BIOMATERIALS SCIENCE & ENGINEERING
Volume 3, Issue 11, Pages 2934-2942

Publisher

AMER CHEMICAL SOC
DOI: 10.1021/acsbiomaterials.6b00693

Keywords

catch bond; acto-myosin assembly; finite elements; cell contraction; mechanosensitivity; hierarchical modeling

Funding

  1. National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health [1R01AR065441]
  2. National Science Foundation under the CAREER award [1350090]
  3. Div Of Civil, Mechanical, & Manufact Inn
  4. Directorate For Engineering [1350090] Funding Source: National Science Foundation

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The contraction and spreading of nonmuscle cells are important phenomena in a number of cellular processes such as differentiation, morphogenesis, and tissue growth. Recent experimental work has shown that the topology and the mechanical properties of the underlying substrate play a significant role in directing the cell's response. In this work, we introduce a multiscale model to understand the sensing, activation, and contraction of the actin cytoskeleton of nonmuscle cells based on the idea that acto-myosin cross bridges display a catch-bond response. After investigating the respective roles of bond catchiness and acto-myosin assembly on the mechano-sensitivity of stress fibers, we present full simulations of cells laying on arrays of micropillars. Model predictions show good qualitative agreements with experimental observation, suggesting that acto-myosin catch bonds are a major mechano-sensing element in nonmuscle cells.

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