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Anisotropy profoundly alters stress fields within contractile cells and cell aggregates

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Abstract

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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Data availability

The data that support the findings within this study can be found in supplementary materials or are available from the corresponding author upon reasonable request.

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Acknowledgements

This work was funded in part by grants from the National Science Foundation (CMMI 1761432), the National Institutes of Health (2R15HL087257-02A1), and a Worcester Polytechnic Institute/University of Massachusetts Medical School Seed Grant. HAC, NR, and KLB designed the problem. HAC developed the analytical framework. HAC performed the numerical analysis. HAC, NR, and KLB interpreted the results. HAC wrote the manuscript. HAC, KLB, and NR revised the manuscript. Heather AC, and ZE Goldblatt are acknowledged for providing permission to use their results in Fig. 1a, b. Sina Askarinejad is acknowledged for providing insight on numerical modeling. The authors declare no competing financial interests. All the data that support the findings within this study can be found in Supplementary Information or are available from the corresponding author upon reasonable request.

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Authors and Affiliations

  1. Department of Civil and Environmental Engineering, Worcester Polytechnic Institute, 100 Institute Rd, Worcester, MA, 01609, USA

    Habibeh Ashouri Choshali & Nima Rahbar

  2. Department of Biomedical Engineering, Worcester Polytechnic Institute, 100 Institute Rd, Worcester, MA, 01609, USA

    Kristen L. Billiar

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  1. Habibeh Ashouri Choshali
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  2. Kristen L. Billiar
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  3. Nima Rahbar
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Correspondence to Nima Rahbar.

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Ashouri Choshali, H., Billiar, K.L. & Rahbar, N. Anisotropy profoundly alters stress fields within contractile cells and cell aggregates. Biomech Model Mechanobiol 21, 1357–1370 (2022). https://doi.org/10.1007/s10237-022-01595-0

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