Department of Mechanical Engineering, University of Sheffield, Sheffield, United Kingdom.
Biomaterials. 2013 Aug;34(26):6119-26. doi: 10.1016/j.biomaterials.2013.04.022. Epub 2013 May 21.
Several computational models based on experimental techniques and theories have been proposed to describe cytoskeleton (CSK) mechanics. Tensegrity is a prominent model for force generation, but it cannot predict mechanics of individual CSK components, nor explain the discrepancies from the different single cell stimulating techniques studies combined with cytoskeleton-disruptors. A new numerical concept that defines a multi-structural 3D finite element (FE) model of a single-adherent cell is proposed to investigate the biophysical and biochemical differences of the mechanical role of each cytoskeleton component under loading. The model includes prestressed actin bundles and microtubule within cytoplasm and nucleus surrounded by the actin cortex. We performed numerical simulations of atomic force microscopy (AFM) experiments by subjecting the cell model to compressive loads. The numerical role of the CSK components was corroborated with AFM force measurements on U2OS-osteosarcoma cells and NIH-3T3 fibroblasts exposed to different cytoskeleton-disrupting drugs. Computational simulation showed that actin cortex and microtubules are the major components targeted in resisting compression. This is a new numerical tool that explains the specific role of the cortex and overcomes the difficulty of isolating this component from other networks in vitro. This illustrates that a combination of cytoskeletal structures with their own properties is necessary for a complete description of cellular mechanics.
已经提出了几种基于实验技术和理论的计算模型来描述细胞骨架（CSK）力学。张紧结构是一种用于产生力的突出模型，但它不能预测单个 CSK 组件的力学特性，也不能解释来自不同单细胞刺激技术研究的差异，这些研究结合了细胞骨架破坏剂。提出了一种新的数值概念，定义了单个附着细胞的多结构 3D 有限元（FE）模型，以研究在加载下每个细胞骨架组件的机械作用的生物物理和生化差异。该模型包括细胞质和细胞核内的预应力肌动蛋白束和微管，并被肌动蛋白皮层包围。我们通过对细胞模型施加压缩载荷来进行原子力显微镜（AFM）实验的数值模拟。通过对暴露于不同细胞骨架破坏药物的 U2OS 骨肉瘤细胞和 NIH-3T3 成纤维细胞进行 AFM 力测量，验证了 CSK 组件的数值作用。计算模拟表明，肌动蛋白皮层和微管是抵抗压缩的主要目标组件。这是一种新的数值工具，它解释了皮层的特定作用，并克服了在体外将该组件与其他网络分离的困难。这表明，细胞骨架结构及其自身特性的组合对于完整描述细胞力学是必要的。
