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Cellular Orientation Is Guided by Strain Gradients

Sophie Chagnon-Lessard, Hubert Jean-Ruel, Michel Godin, Andrew E. Pelling
doi: https://doi.org/10.1101/095976
Sophie Chagnon-Lessard
aDepartment of Physics, Center for Interdisciplinary Nanophysics, 598 King Edward, University of Ottawa, Ottawa, ON, K1N 6N5, Canada. Email: ; Fax: +1 (613) 562-5190; Tel: +1 (613) 562-5800, (6965)
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  • For correspondence: a@pellinglab.ne
Hubert Jean-Ruel
bDepartment of Electronics, 1125 Colonel By Drive, Carleton University, Ottawa, ON, K1S 5B6
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Michel Godin
aDepartment of Physics, Center for Interdisciplinary Nanophysics, 598 King Edward, University of Ottawa, Ottawa, ON, K1N 6N5, Canada. Email: ; Fax: +1 (613) 562-5190; Tel: +1 (613) 562-5800, (6965)
cDepartment of Mechanical Engineering, Site Building, 800 King Edward Avenue, University of Ottawa, Ottawa, ON, K1N 6N5, Canada
dOttawa-Carleton Institute for Biomedical Engineering, Ottawa, Ontario, K1N 6N5, Canada
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  • For correspondence: a@pellinglab.ne
Andrew E. Pelling
aDepartment of Physics, Center for Interdisciplinary Nanophysics, 598 King Edward, University of Ottawa, Ottawa, ON, K1N 6N5, Canada. Email: ; Fax: +1 (613) 562-5190; Tel: +1 (613) 562-5800, (6965)
eDepartment of Biology, Gendron Hall, 30 Marie Curie, University of Ottawa, Ottawa, ON, K1N 6N5, Canada
fInstitute for Science, Society and Policy, Desmarais Building, 55 Laurier Ave. East, University of Ottawa, Ottawa, ON, K1N 6N5, Canada
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  • For correspondence: a@pellinglab.ne
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Abstract

The strain-induced reorientation response of cyclically stretched cells has been well characterized in uniform strain fields. In the present study, we comprehensively analyse the behaviour of human fibroblasts subjected to a highly non-uniform strain field within a polymethylsiloxane microdevice. Our results indicate that the strain gradient amplitude and direction regulate cell reorientation through a coordinated gradient avoidance response. We provide critical evidence that strain gradient is a key physical cue that can guide cell organization. Specifically, our work suggests that cells are able to pinpoint the location under the cell of multiple physical cues and integrate this information (strain and strain gradient amplitudes and directions), resulting in a coordinated response. To gain insight into the underlying mechanosensing processes, we studied focal adhesion reorganization and the effect of modulating myosin-II contractility. The extracted focal adhesion orientation distributions are similar to those obtained for the cell bodies, and their density is increased by the presence of stretching forces. Moreover, it was found that the myosin-II activity promoter calyculin-A has little effect on the cellular response, while the inhibitor blebbistatin suppresses cell and focal adhesion alignment and reduces focal adhesion density. These results confirm that similar internal structures involved in sensing and responding to strain direction and amplitude are also key players in strain gradient mechanosensing and avoidance.

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Posted May 12, 2017.
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Cellular Orientation Is Guided by Strain Gradients
Sophie Chagnon-Lessard, Hubert Jean-Ruel, Michel Godin, Andrew E. Pelling
bioRxiv 095976; doi: https://doi.org/10.1101/095976
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Cellular Orientation Is Guided by Strain Gradients
Sophie Chagnon-Lessard, Hubert Jean-Ruel, Michel Godin, Andrew E. Pelling
bioRxiv 095976; doi: https://doi.org/10.1101/095976

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