CUED Publications database

Role of boundary conditions in determining cell alignment in response to stretch

Deshpande, VS (2017) Role of boundary conditions in determining cell alignment in response to stretch. Proceedings of the National Academy of Sciences of the United States of America, 115. pp. 986-991.

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he ability of cells to orient in response to mechanical stimuli is essential to embryonic development, cell migration, mechanotrans- duction, and other critical physiologic functions in a range of organs. Endothelial cells, fibroblasts, mesenchymal stem cells, and osteo- blasts all orient perpendicular to an applied cyclic stretch when plated on stretchable elastic substrates, suggesting a common underlying mechanism. However, many of these same cells orient parallel to stretch in vivo and in 3D culture, and a compelling explanation for the different orientation responses in 2D and 3D has remained elusive. Here, we used an experimental system to conduct a series of experiments designed specifically to test the hypothesis that differences in strains transverse to the primary loading direc- tion give rise to the different alignment patterns observed in 2D and 3D cyclic stretch experiments (“strain avoidance”). We found that, in static or low-frequency stretch conditions, cell alignment in fibroblast-populated collagen gels correlated with the presence or absence of a restraining boundary condition rather than with compaction strains. Cyclic stretch could induce perpendicular align- ment in 3D culture but only at frequencies an order of magnitude greater than reported to induce perpendicular alignment in 2D. We modified a published model of stress fiber dynamics and were able to reproduce our experimental findings across all conditions tested as well as published data from 2D cyclic stretch experiments. These experimental and model results suggest an explanation for the ap- parently contradictory alignment responses of cells subjected to cyclic stretch on 2D membranes and in 3D gels.

Item Type: Article
Uncontrolled Keywords: cell mechanics cytoskeleton stress fibers computational modeling fibroblast orientation
Divisions: Div C > Materials Engineering
Div C > Applied Mechanics
Depositing User: Cron Job
Date Deposited: 13 Jan 2018 20:06
Last Modified: 15 Sep 2020 05:28
DOI: 10.1073/pnas.1715059115