Liu Yi, Mollaeian Keyvan, Ren Juan
Department of Mechanical Engineering, Iowa State University, Ames, IA 50011, USA.
Department of Mechanical Engineering, Iowa State University, Ames, IA 50011, USA.
Micron. 2019 Jan;116:108-115. doi: 10.1016/j.micron.2018.10.004. Epub 2018 Oct 14.
Mechanotransduction-the process living cells sense and respond to forces-is essential for maintenance of normal cell, tissue, and organ functioning. To promote the knowledge of mechanotransduction, atomic force microscope (AFM) force-indentation has been broadly used to quantify the mechanical properties of living cells. However, most studies treated the cells as a homogeneous elastic or viscoelastic material, which is far from the real structure of cells, and the quantified mechanical properties cannot be used to investigate the inner working mechanism of mechanotransduction, such as internal force distribution/transduction. Therefore, a new viscoelastic finite element method (FEM) model is proposed in this study to simulate the force response of living cells during AFM force-indentation measurement by accounting for both the cell elasticity and viscoelasticity. The cell is modeled as a multi-layered structure with different mechanical characteristics of each layer to account for the depth-dependent mechanical behavior of living cells. This FEM model was validated by comparing the simulated force-indentation curves with the AFM experimental data on living NIH/3T3 cells, and the simulation error was less than 10% with respect to the experiment results. Therefore, the proposed FEM model can accurately simulate the force response of living cells and has a potential to be utilized to study and predict the intracellular force transduction and distribution.
力传导——活细胞感知并响应力的过程——对于维持正常的细胞、组织和器官功能至关重要。为了增进对力传导的了解，原子力显微镜（AFM）力压痕技术已被广泛用于量化活细胞的力学特性。然而，大多数研究将细胞视为均匀的弹性或粘弹性材料，这与细胞的真实结构相差甚远，而且量化的力学特性无法用于研究力传导的内部工作机制，如内力分布/传导。因此，本研究提出了一种新的粘弹性有限元方法（FEM）模型，通过考虑细胞的弹性和粘弹性来模拟AFM力压痕测量过程中活细胞的力响应。将细胞建模为具有不同力学特性的多层结构，以考虑活细胞深度依赖的力学行为。通过将模拟的力压痕曲线与活的NIH/3T3细胞的AFM实验数据进行比较，验证了该有限元模型，模拟误差相对于实验结果小于10%。因此，所提出的有限元模型能够准确模拟活细胞的力响应，具有研究和预测细胞内力传导和分布的潜力。
