Program in Molecular and Integrative Physiological Sciences, Department of Environmental Health, Harvard School of Public Health, Boston, MA 02115, USA.
Biomech Model Mechanobiol. 2012 Sep;11(7):1075-84. doi: 10.1007/s10237-012-0374-y. Epub 2012 Feb 4.
Physical forces can elicit complex time- and space-dependent deformations in living cells. These deformations at the subcellular level are difficult to measure but can be estimated using computational approaches such as finite element (FE) simulation. Existing FE models predominantly treat cells as spring-dashpot viscoelastic materials, while broad experimental data are now lending support to the power-law rheology (PLR) model. Here, we developed a large deformation FE model that incorporated PLR and experimentally verified this model by performing micropipette aspiration on fibroblasts under various mechanical loadings. With a single set of rheological properties, this model recapitulated the diverse micropipette aspiration data obtained using three protocols and with a range of micropipette sizes. More intriguingly, our analysis revealed that decreased pipette size leads to increased pressure gradient, potentially explaining our previous counterintuitive finding that decreased pipette size leads to increased incidence of cell blebbing and injury. Taken together, our work leads to more accurate rheological interpretation of micropipette aspiration experiments than previous models and suggests pressure gradient as a potential determinant of cell injury.
物理力可以在活细胞中引起复杂的随时间和空间变化的变形。这些亚细胞水平的变形很难测量，但可以使用计算方法（如有限元（FE）模拟）来估计。现有的 FE 模型主要将细胞视为弹簧-阻尼粘弹性材料，而广泛的实验数据现在支持幂律流变（PLR）模型。在这里，我们开发了一个大变形 FE 模型，该模型包含了 PLR，并通过在各种机械载荷下对成纤维细胞进行微管吸吮实验来验证该模型。通过一组流变特性，该模型再现了使用三种方案和不同微管尺寸获得的各种微管吸吮数据。更有趣的是，我们的分析表明，微管尺寸的减小会导致压力梯度增加，这可能解释了我们之前的反直觉发现，即微管尺寸的减小会导致细胞起泡和损伤的发生率增加。总之，我们的工作比以前的模型更准确地解释了微管吸吮实验的流变学，并提出了压力梯度作为细胞损伤的一个潜在决定因素。
