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计算模型结合体外实验分析间充质干细胞黏附过程中的力转导。

Computational model combined with in vitro experiments to analyse mechanotransduction during mesenchymal stem cell adhesion.

机构信息

Institute of Movement Sciences, Aix-Marseille Univ, CNRS UMR 7287, F-13288 Marseille, France.

出版信息

Eur Cell Mater. 2013 Jan 16;25:97-113. doi: 10.22203/ecm.v025a07.

DOI:10.22203/ecm.v025a07
PMID:23325541
Abstract

The shape that stem cells reach at the end of adhesion process influences their differentiation. Rearrangement of cytoskeleton and modification of intracellular tension may activate mechanotransduction pathways controlling cell commitment. In the present study, the mechanical signals involved in cell adhesion were computed in in vitro stem cells of different shapes using a single cell model, the so-called Cytoskeleton Divided Medium (CDM) model. In the CDM model, the filamentous cytoskeleton and nucleoskeleton networks were represented as a mechanical system of multiple tensile and compressive interactions between the nodes of a divided medium. The results showed that intracellular tonus, focal adhesion forces as well as nuclear deformation increased with cell spreading. The cell model was also implemented to simulate the adhesion process of a cell that spreads on protein-coated substrate by emitting filopodia and creating new distant focal adhesion points. As a result, the cell model predicted cytoskeleton reorganisation and reinforcement during cell spreading. The present model quantitatively computed the evolution of certain elements of mechanotransduction and may be a powerful tool for understanding cell mechanobiology and designing biomaterials with specific surface properties to control cell adhesion and differentiation.

摘要

细胞黏附过程结束时细胞的形状会影响其分化。细胞骨架的重排和细胞内张力的改变可能会激活控制细胞定向分化的机械转导途径。在本研究中,使用单细胞模型,即所谓的细胞骨架分割介质(CDM)模型,计算了不同形状的体外干细胞中参与细胞黏附的力学信号。在 CDM 模型中,丝状细胞骨架和核骨架网络被表示为一个由分割介质节点之间的多个拉伸和压缩相互作用组成的力学系统。结果表明,细胞扩展时细胞内张力、黏附力和核变形都会增加。该细胞模型还被用于模拟细胞在蛋白包被的基底上黏附的过程,即通过发射丝状伪足和创建新的远距离黏附点。结果表明,细胞模型预测了细胞扩展过程中细胞骨架的重组和强化。该模型定量计算了机械转导某些元素的演变,可能是理解细胞机械生物学和设计具有特定表面特性的生物材料以控制细胞黏附和分化的有力工具。

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