4.5 Article

Anisotropy profoundly alters stress fields within contractile cells and cell aggregates

Journal

BIOMECHANICS AND MODELING IN MECHANOBIOLOGY
Volume 21, Issue 5, Pages 1357-1370

Publisher

SPRINGER HEIDELBERG
DOI: 10.1007/s10237-022-01595-0

Keywords

Anisotropic contractility; Circular constrained cells; Mechanical stress; Stress-biomarker relations

Funding

  1. National Science Foundation [CMMI 1761432]
  2. National Institutes of Health [2R15HL087257-02A1]
  3. Worcester Polytechnic Institute/University of Massachusetts Medical School Seed Grant

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In this study, the stress fields within cells were investigated using computational and experimental methods, revealing the presence of anisotropy. It was found that substantial stress concentration occurs in the central region, contradicting the assumption of uniform anisotropy. A more realistic non-uniform anisotropy model was introduced based on experimental observations, effectively eliminating stress concentration. The study provides a physics-based mechanism to explain the low alignment of stress fibers in cells and potentially explains certain biological phenomena.
Many biological phenomena such as cell proliferation and death are correlated with stress fields within cells. Stress fields are quantified using computational methods which rely on fundamental assumptions about local mechanical properties. Most existing methods such as Monolayer Stress Microscopy assume isotropic properties, yet experimental observations strongly suggest anisotropy. We first model anisotropy in circular cells analytically using Eshelby's inclusion method. Our solution reveals that uniform anisotropy cannot exist in cells due to the occurrence of substantial stress concentration in the central region. A more realistic non-uniform anisotropy model is then introduced based on experimental observations and implemented numerically which interestingly clears out stress concentration. Stresses within the entire aggregate also drastically change compared to the isotropic case, resulting in better agreement with observed biomarkers. We provide a physics-based mechanism to explain the low alignment of stress fibers in the center of cells, which might explain certain biological phenomena e.g., existence of disrupted rounded cells, and higher apoptosis rate at the center of circular aggregates.

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