Entropic forces drive cellular contact guidance

Antonetta B.C. Buskermolen, Hamsini Suresh, Siamak S. Shishvan, Andrea Vigliotti, Antonio DeSimone, Nicholas A. Kurniawan, Carlijn V.C. Bouten, Vikram S. Deshpande (Corresponding author)

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Contact guidance-the widely known phenomenon of cell alignment induced by anisotropic environmental features-is an essential step in the organization of adherent cells, but the mechanisms by which cells achieve this orientational ordering remain unclear. Here, we seeded myofibroblasts on substrates micropatterned with stripes of fibronectin and observed that contact guidance emerges at stripe widths much greater than the cell size. To understand the origins of this surprising observation, we combined morphometric analysis of cells and their subcellular components with a, to our knowledge, novel statistical framework for modeling nonthermal fluctuations of living cells. This modeling framework is shown to predict not only the trends but also the statistical variability of a wide range of biological observables, including cell (and nucleus) shapes, sizes, and orientations, as well as stress-fiber arrangements within the cells with remarkable fidelity with a single set of cell parameters. By comparing observations and theory, we identified two regimes of contact guidance: 1) guidance on stripe widths smaller than the cell size (w ≤ 160 μm), which is accompanied by biochemical changes within the cells, including increasing stress-fiber polarization and cell elongation; and 2) entropic guidance on larger stripe widths, which is governed by fluctuations in the cell morphology. Overall, our findings suggest an entropy-mediated mechanism for contact guidance associated with the tendency of cells to maximize their morphological entropy through shape fluctuations.

LanguageEnglish
Pages1994-2008
Number of pages15
JournalBiophysical Journal
Volume116
Issue number10
Early online date10 Apr 2019
DOIs
StatePublished - 21 May 2019

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Stress Fibers
Entropy
Cell Size
Cell Nucleus Shape
Cell Nucleus Size
Myofibroblasts
Fibronectins
Observation

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Buskermolen, A. B. C., Suresh, H., Shishvan, S. S., Vigliotti, A., DeSimone, A., Kurniawan, N. A., ... Deshpande, V. S. (2019). Entropic forces drive cellular contact guidance. Biophysical Journal, 116(10), 1994-2008. DOI: 10.1016/j.bpj.2019.04.003
Buskermolen, Antonetta B.C. ; Suresh, Hamsini ; Shishvan, Siamak S. ; Vigliotti, Andrea ; DeSimone, Antonio ; Kurniawan, Nicholas A. ; Bouten, Carlijn V.C. ; Deshpande, Vikram S./ Entropic forces drive cellular contact guidance. In: Biophysical Journal. 2019 ; Vol. 116, No. 10. pp. 1994-2008
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Buskermolen, ABC, Suresh, H, Shishvan, SS, Vigliotti, A, DeSimone, A, Kurniawan, NA, Bouten, CVC & Deshpande, VS 2019, 'Entropic forces drive cellular contact guidance' Biophysical Journal, vol. 116, no. 10, pp. 1994-2008. DOI: 10.1016/j.bpj.2019.04.003

Entropic forces drive cellular contact guidance. / Buskermolen, Antonetta B.C.; Suresh, Hamsini; Shishvan, Siamak S.; Vigliotti, Andrea; DeSimone, Antonio; Kurniawan, Nicholas A.; Bouten, Carlijn V.C.; Deshpande, Vikram S. (Corresponding author).

In: Biophysical Journal, Vol. 116, No. 10, 21.05.2019, p. 1994-2008.

Research output: Contribution to journalArticleAcademicpeer-review

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N2 - Contact guidance-the widely known phenomenon of cell alignment induced by anisotropic environmental features-is an essential step in the organization of adherent cells, but the mechanisms by which cells achieve this orientational ordering remain unclear. Here, we seeded myofibroblasts on substrates micropatterned with stripes of fibronectin and observed that contact guidance emerges at stripe widths much greater than the cell size. To understand the origins of this surprising observation, we combined morphometric analysis of cells and their subcellular components with a, to our knowledge, novel statistical framework for modeling nonthermal fluctuations of living cells. This modeling framework is shown to predict not only the trends but also the statistical variability of a wide range of biological observables, including cell (and nucleus) shapes, sizes, and orientations, as well as stress-fiber arrangements within the cells with remarkable fidelity with a single set of cell parameters. By comparing observations and theory, we identified two regimes of contact guidance: 1) guidance on stripe widths smaller than the cell size (w ≤ 160 μm), which is accompanied by biochemical changes within the cells, including increasing stress-fiber polarization and cell elongation; and 2) entropic guidance on larger stripe widths, which is governed by fluctuations in the cell morphology. Overall, our findings suggest an entropy-mediated mechanism for contact guidance associated with the tendency of cells to maximize their morphological entropy through shape fluctuations.

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Buskermolen ABC, Suresh H, Shishvan SS, Vigliotti A, DeSimone A, Kurniawan NA et al. Entropic forces drive cellular contact guidance. Biophysical Journal. 2019 May 21;116(10):1994-2008. Available from, DOI: 10.1016/j.bpj.2019.04.003