Finite element analysis of traction force microscopy: influence of cell mechanics, adhesion, and morphology.
Finite element analysis of traction force microscopy: influence of cell mechanics, adhesion, and morphology.
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DOI：
10.1115/1.4024467
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发表时间：
2013-07
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影响因子：
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通讯作者：
Rachel Zielinski;C. Mihai;D. Kniss;S. Ghadiali
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文献类型：
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作者：
Rachel Zielinski;C. Mihai;D. Kniss;S. Ghadiali
贴壁细胞与其细胞外基质（ECM）之间的相互作用在许多生物学过程中起着重要作用，如伤口愈合、形态发生、分化和细胞迁移。细胞附着于ECM的粘着斑，并通过细胞骨架肌动蛋白应力纤维将收缩力传递给基质。这种收缩导致基底/ECM内的牵引应力。牵引力显微镜（TFM）是一种用于量化贴壁细胞产生的收缩力的实验技术。在TFM中，将细胞接种在柔性基底上，并且跟踪由细胞收缩引起的基底的位移并将其转换为牵引应力场。这些牵引应力的大小通常用作内部细胞收缩力或收缩性的替代量度。我们假设，除了收缩力，其他生物力学特性，包括细胞刚度，粘附能量密度，和细胞形态可能会影响牵引应力测量TFM。在这项研究中，我们开发了2D和3D TFM技术的有限元模型，以研究几种生物力学特性的变化如何改变TFM测量的牵引应力。我们独立地改变细胞刚度、细胞-ECM粘附能量密度、细胞纵横比和收缩性，并进行敏感性分析，以确定哪些参数对测得的最大牵引应力和净收缩力矩有显著影响。结果表明，细胞刚度和粘附能量密度的变化可以显着改变测量牵引力，独立的收缩性。基于敏感性分析，我们开发了一个校正因子来解释细胞刚度和粘附力的变化，并成功地将此校正因子算法应用于侵袭性和非侵袭性癌细胞的实验TFM测量。因此，将这些类型的校正应用于TFM测量可以产生细胞收缩性的更准确的估计。
The interactions between adherent cells and their extracellular matrix (ECM) have been shown to play an important role in many biological processes, such as wound healing, morphogenesis, differentiation, and cell migration. Cells attach to the ECM at focal adhesion sites and transmit contractile forces to the substrate via cytoskeletal actin stress fibers. This contraction results in traction stresses within the substrate/ECM. Traction force microscopy (TFM) is an experimental technique used to quantify the contractile forces generated by adherent cells. In TFM, cells are seeded on a flexible substrate and displacements of the substrate caused by cell contraction are tracked and converted to a traction stress field. The magnitude of these traction stresses are normally used as a surrogate measure of internal cell contractile force or contractility. We hypothesize that in addition to contractile force, other biomechanical properties including cell stiffness, adhesion energy density, and cell morphology may affect the traction stresses measured by TFM. In this study, we developed finite element models of the 2D and 3D TFM techniques to investigate how changes in several biomechanical properties alter the traction stresses measured by TFM. We independently varied cell stiffness, cell-ECM adhesion energy density, cell aspect ratio, and contractility and performed a sensitivity analysis to determine which parameters significantly contribute to the measured maximum traction stress and net contractile moment. Results suggest that changes in cell stiffness and adhesion energy density can significantly alter measured tractions, independent of contractility. Based on a sensitivity analysis, we developed a correction factor to account for changes in cell stiffness and adhesion and successfully applied this correction factor algorithm to experimental TFM measurements in invasive and noninvasive cancer cells. Therefore, application of these types of corrections to TFM measurements can yield more accurate estimates of cell contractility.