Harnessing traction-mediated manipulation of the cell/matrix interface to control stem-cell fate.
Harnessing traction-mediated manipulation of the cell/matrix interface to control stem-cell fate.
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作者：
干细胞感知并响应细胞外基质的机械特性。然而，细胞外基质力学在3D微环境中影响干细胞命运的程度和潜在的生物物理机制尚不清楚。我们证明了间充质干细胞（MSC）群体的承诺响应于3D微环境的刚性而变化，成骨主要发生在11-30 kPa。然而，与以前的2D工作相反，细胞命运与形态学无关。相反，基质硬度调节整合素结合以及重组的粘附配体的纳米级，这两者都是牵引依赖性和相关的成骨承诺的MSC人口。这些发现表明，细胞将粘附基质的物理性质的变化解释为粘附配体呈递的变化，并且细胞本身可以被利用为工具，将材料机械加工成反馈以操纵其命运的结构。
Stem cells sense and respond to the mechanical properties of the extracellular matrix. However, both the extent to which extracellular matrix mechanics affect stem cell fate in 3D micro-environments and the underlying biophysical mechanisms are unclear. We demonstrate that the commitment of mesenchymal stem cell (MSC) populations changes in response to the rigidity of 3D micro-environments, with osteogenesis occurring predominantly at 11–30 kPa. In contrast to previous 2D work, however, cell fate was not correlated with morphology. Instead, matrix stiffness regulated integrin binding as well as reorganization of adhesion ligands on the nanoscale, both of which were traction-dependent and correlated with osteogenic commitment of MSC populations. These findings suggest that cells interpret changes in the physical properties of adhesion substrates as changes in adhesion ligand presentation, and that cells themselves can be harnessed as tools to mechanically process materials into structures that feedback to manipulate their fate.
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DOI：
10.1073/pnas.0808932106
发表时间：
2009-01-13
影响因子：
11.1
作者：
Fischbach, Claudia;Kong, Hyun Joon;Mooney, David J.
通讯作者：
Mooney, David J.
影响因子：
56.9
作者：
Cukierman, E;Pankov, R;Yamada, KM
通讯作者：
Yamada, KM
影响因子：
3.4
作者：
Engler, A;Bacakova, L;Discher, D
通讯作者：
Discher, D
DOI：
10.2106/00004623-199301000-00012
发表时间：
1993-01-01
影响因子：
5.3
作者：
DIDUCH, DR;COE, MR;BALIAN, G
通讯作者：
BALIAN, G
DOI：
10.1073/pnas.192291499
发表时间：
2002-09-17
影响因子：
11.1
作者：
Alsberg, E;Anderson, KW;Mooney, DJ
通讯作者：
Mooney, DJ