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学信号转导
Computational model combined with in vitro experiments to analyse mechanotransduction during mesenchymal stem cell adhesion
摘要：
干细胞在粘附过程结束时达到的形状影响其分化。细胞骨架的重排和细胞内张力的改变可以激活控制细胞定型的机械传导通路。在本研究中，机械信号参与细胞黏附计算在体外干细胞的不同形状的使用单细胞模型，所谓的细胞骨架划分介质（CDM）模型。在CDM模型中，丝状的细胞骨架和核骨架网络被表示为一个力学系统的多个拉伸和压缩的节点之间的相互作用，一个分开的介质。结果表明，随着细胞伸展，细胞内张力、粘着斑力和核变形均增加。该细胞模型还被实现来模拟细胞的粘附过程，该细胞通过发射丝状伪足和创建新的远距离粘着焦点而在蛋白质涂覆的基底上扩散。因此，细胞模型预测细胞骨架重组和加强在细胞扩散。本模型定量计算的某些元素的mechanotransduction的演变，并可能是一个强大的工具，了解细胞的机械生物学和设计生物材料的特定表面特性，以控制细胞黏附和分化。
英文摘要：
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.
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