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Shifting the optimal stiffness for cell migration

Bangasser, BL
Shamsan, GA
Chan, CE
Opoku, KN
Tüzel, E
Schlichtmann, BW
Kasim, JA
Fuller, BJ
McCullough, BR
Rosenfeld, SS
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10.1038/ncomms15313
Abstract
© The Author(s) 2017. Cell migration, which is central to many biological processes including wound healing and cancer progression, is sensitive to environmental stiffness, and many cell types exhibit a stiffness optimum, at which migration is maximal. Here we present a cell migration simulator that predicts a stiffness optimum that can be shifted by altering the number of active molecular motors and clutches. This prediction is verified experimentally by comparing cell traction and F-actin retrograde flow for two cell types with differing amounts of active motors and clutches: embryonic chick forebrain neurons (ECFNs; optimum ∼ 1 kPa) and U251 glioma cells (optimum ∼ 100 kPa). In addition, the model predicts, and experiments confirm, that the stiffness optimum of U251 glioma cell migration, morphology and F-actin retrograde flow rate can be shifted to lower stiffness by simultaneous drug inhibition of myosin II motors and integrin-mediated adhesions.
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Springer Science and Business Media LLC
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Nature Communications
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