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Nat Commun ; 8: 15313, 2017 05 22.
Article in English | MEDLINE | ID: mdl-28530245

ABSTRACT

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.


Subject(s)
Actins/metabolism , Cell Movement , Glioma/pathology , Neurons/cytology , Prosencephalon/pathology , Actin Cytoskeleton/metabolism , Algorithms , Animals , Cell Adhesion , Cell Line, Tumor , Chick Embryo , Collagen/chemistry , Disease Progression , Elastic Modulus , Humans , Integrins/metabolism , Mice , Models, Biological , Models, Statistical , Myosin Type II/metabolism , RNA, Messenger/metabolism
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