Cell shape information is transduced through tension-independent mechanisms

Amit Ron, Evren U. Azeloglu, Rhodora C. Calizo, Mufeng Hu, Smiti Bhattacharya, Yibang Chen, Gomathi Jayaraman, Sunwoo Lee, Susana R. Neves-Zaph, Hong Li, Ronald E. Gordon, John C. He, James C. Hone () and Ravi Iyengar ()
Additional contact information
Amit Ron: Columbia University
Evren U. Azeloglu: Icahn School of Medicine at Mount Sinai
Rhodora C. Calizo: Icahn School of Medicine at Mount Sinai
Mufeng Hu: Columbia University
Smiti Bhattacharya: Columbia University
Yibang Chen: Icahn School of Medicine at Mount Sinai
Gomathi Jayaraman: Icahn School of Medicine at Mount Sinai
Sunwoo Lee: Cornell University
Susana R. Neves-Zaph: Icahn School of Medicine at Mount Sinai
Hong Li: Biochemistry and Molecular Genetics, Rutgers University – New Jersey Medical School
Ronald E. Gordon: Icahn School of Medicine at Mount Sinai
John C. He: Icahn School of Medicine at Mount Sinai
James C. Hone: Columbia University
Ravi Iyengar: Icahn School of Medicine at Mount Sinai

Nature Communications, 2017, vol. 8, issue 1, 1-15

Abstract: Abstract The shape of a cell within tissues can represent the history of chemical and physical signals that it encounters, but can information from cell shape regulate cellular phenotype independently? Using optimal control theory to constrain reaction-diffusion schemes that are dependent on different surface-to-volume relationships, we find that information from cell shape can be resolved from mechanical signals. We used microfabricated 3-D biomimetic chips to validate predictions that shape-sensing occurs in a tension-independent manner through integrin β3 signaling pathway in human kidney podocytes and smooth muscle cells. Differential proteomics and functional ablation assays indicate that integrin β3 is critical in transduction of shape signals through ezrin–radixin–moesin (ERM) family. We used experimentally determined diffusion coefficients and experimentally validated simulations to show that shape sensing is an emergent cellular property enabled by multiple molecular characteristics of integrin β3. We conclude that 3-D cell shape information, transduced through tension-independent mechanisms, can regulate phenotype.

Date: 2017
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DOI: 10.1038/s41467-017-02218-4

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