Shifting the optimal stiffness for cell migration

被引：243

作者：

Bangasser, Benjamin L. ^{[1
]}

Shamsan, Ghaidan A. ^{[1
]}

Chan, Clarence E. ^{[1
]}

Opoku, Kwaku N. ^{[1
]}

Tuzel, Erkan ^{[1
,3
]}

Schlichtmann, Benjamin W. ^{[1
]}

Kasim, Jesse A. ^{[1
]}

Fuller, Benjamin J. ^{[1
]}

McCullough, Brannon R. ^{[1
,4
]}

Rosenfeld, Steven S. ^{[2
]}

Odde, David J. ^{[1
]}

机构：

[1] Univ Minnesota, Dept Biomed Engn, 312 Church St SE, Minneapolis, MN 55455 USA

[2] Cleveland Clin, Brain Tumor & Neurooncol Ctr, 9500 Euclid Ave, Cleveland, OH 44195 USA

[3] Worcester Polytech Inst, Dept Phys, 100 Inst Rd, Worcester, MA 01609 USA

[4] No Arizona Univ, Dept Chem & Biochem, 700 S Osborne Dr, Flagstaff, AZ 86011 USA

来源：

NATURE COMMUNICATIONS | 2017年 / 8卷

基金：

美国国家科学基金会; 美国国家卫生研究院;

关键词：

MOTOR-CLUTCH MODEL; FORCE TRANSMISSION; TRACTION; ADHESION; RIGIDITY; MATRIX; ACTIN; SUBSTRATE; MOVEMENT; DYNAMICS;

D O I：

10.1038/ncomms15313

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

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 similar to 1 kPa) and U251 glioma cells (optimum similar to 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.

引用

页数：10

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