Micromechanical control of cell-cell interactions

Micromechanical control of cell-cell interactions
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DOI:
10.1073/pnas.0608660104
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发表时间:
2007-04-03
影响因子:
11.1
通讯作者:
Bhatia, Sangeeta N.
Bhatia, Sangeeta N.
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Hui, Elliot E.;Bhatia, Sangeeta N.

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活组织的发育和功能在很大程度上取决于细胞之间的相互作用,这些相互作用可以在时间和空间上变化;然而,细胞间相互作用的时间控制在实验上具有挑战性。通过使用具有移动部件的微加工硅衬底,我们展示了通过以微米级精度直接操纵粘附细胞来动态调节细胞-细胞相互作用。因此,我们实现了对组织组成和空间组织的机械控制。作为一个案例研究,我们证明了这个工具的效用,在解构动态的肝细胞和支持性基质细胞共培养之间的细胞间通讯。我们的研究结果表明,基质维持肝细胞表型需要在有限的时间内(约数小时)直接接触,然后是持续的可溶性信号,其有效范围为:
The development and function of living tissues depends largely on interactions between cells that can vary in both time and space; however, temporal control of cell-cell interaction is experimentally challenging. By using a micromachined silicon substrate with moving parts, we demonstrate the dynamic regulation of cell-cell interactions via direct manipulation of adherent cells with micrometer-scale precision. We thereby achieve mechanical control of both tissue composition and spatial organization. As a case study, we demonstrate the utility of this tool in deconstructing the dynamics of intercellular communication between hepatocytes and supportive stromal cells in coculture. Our findings indicate that the maintenance of the hepatocellular phenotype by stroma requires direct contact for a limited time (approximate to hours) followed by a sustained soluble signal that has an effective range of