Cell-geometry-dependent changes in plasma membrane order direct stem cell signalling and fate

被引：164

作者：

von Erlach, Thomas C. ^{[1
,2
,3
]}

Bertazzo, Sergio ^{[1
,4
]}

Wozniak, Michele A. ^{[5
]}

Horejs, Christine-Maria ^{[1
,2
,3
]}

Maynard, Stephanie A. ^{[1
,2
,3
]}

Attwood, Simon ^{[2
]}

Robinson, Benjamin K. ^{[2
]}

Autefage, Helene ^{[1
,2
,3
]}

Kallepitis, Charalambos ^{[1
,2
,3
]}

Hernandez, Armando del Rio ^{[1
]}

Chen, Christopher S. ^{[5
,6
,7
,8
]}

Goldoni, Silvia ^{[1
,2
,3
]}

Stevens, Molly M. ^{[1
,2
,3
]}

机构：

[1] Imperial Coll London, Dept Mat, London, England

[2] Imperial Coll London, Dept Bioengn, London, England

[3] Imperial Coll London, Inst Biomed Engn, London, England

[4] UCL, Dept Med Phys & Biomed Engn, London, England

[5] Univ Penn, Dept Bioengn, Philadelphia, PA 19104 USA

[6] Boston Univ, Dept Bioengn, Boston, MA 02215 USA

[7] Boston Univ, Biol Design Ctr, Boston, MA 02215 USA

[8] Harvard Univ, Wyss Inst Biol Inspired Engn, Boston, MA 02115 USA

来源：

NATURE MATERIALS | 2018年 / 17卷 / 03期

基金：

英国惠康基金; 英国工程与自然科学研究理事会; 欧洲研究理事会;

关键词：

LIPID RAFTS; CAVEOLAE; MICROTUBULES; MICRODOMAINS; GROWTH; SWITCH;

D O I：

10.1038/s41563-017-0014-0

中图分类号：

O64 [物理化学（理论化学）、化学物理学];

学科分类号：

070304 ; 081704 ;

摘要：

Cell size and shape affect cellular processes such as cell survival, growth and differentiation1-4, thus establishing cell geometry as a fundamental regulator of cell physiology. The contributions of the cytoskeleton, specifically actomyosin tension, to these effects have been described, but the exact biophysical mechanisms that translate changes in cell geometry to changes in cell behaviour remain mostly unresolved. Using a variety of innovative materials techniques, we demonstrate that the nanostructure and lipid assembly within the cell plasma membrane are regulated by cell geometry in a ligand-independent manner. These biophysical changes trigger signalling events involving the serine/threonine kinase Akt/protein kinase B (PKB) that direct cell-geometry-dependent mesenchymal stem cell differentiation. Our study defines a central regulatory role by plasma membrane ordered lipid raft microdomains in modulating stem cell differentiation with potential translational applications.

引用

页码：237 / +

页数：8

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