Department of Biomedical Engineering, University of California Irvine, 3120 Natural Sciences II, Irvine, CA 92697-2715, USA.
J Biomech. 2011 Apr 7;44(6):1046-50. doi: 10.1016/j.jbiomech.2011.02.004. Epub 2011 Feb 26.
The attachment of cells to the extracellular matrix (ECM) is achieved by the specific binding of cell-surface receptors to ligands present in the ECM. These interactions are important for many biological processes, including cell migration, cancer development, and wound healing. Our objective was to develop a computational model to investigate how focal adhesion mechanical properties, substrate stiffness, and intracellular stresses affect cell-matrix interactions during cell migration on a flat substrate. In our model, the cell-substrate traction was proportional to the bound receptor concentration, relative velocity between the cell and substrate, and the cell-substrate friction coefficient. Simulation results showed that even if the receptor number and ligand density were fixed, the mechanical properties of the focal adhesions still affected cell-ECM interactions. In fact, the cell-substrate traction was biphasic with respect to the friction coefficient, a parameter that can be used to quantify focal adhesion properties. In contrast, the cell speed was a monotonically decreasing function with respect to this parameter. Furthermore, tractions showed greater increases when the maximum intracellular stress was increased from 400 to 600Pa than when substrate stiffness was increased from 0.5 to 100kPa. This mathematical model is able to quantify the effects of focal adhesion mechanical properties, extracellular stiffness, and intracellular stresses on cell-ECM interactions, and should be beneficial to research in cancer development.
细胞与细胞外基质(ECM)的附着是通过细胞表面受体与 ECM 中存在的配体的特异性结合来实现的。这些相互作用对许多生物过程都很重要,包括细胞迁移、癌症发展和伤口愈合。我们的目标是开发一种计算模型,以研究在平面基底上细胞迁移过程中,粘着斑的力学性质、基底硬度和细胞内应力如何影响细胞与基质的相互作用。在我们的模型中,细胞-基底牵引力与结合的受体浓度、细胞与基底之间的相对速度以及细胞-基底摩擦系数成正比。模拟结果表明,即使受体数量和配体密度固定,粘着斑的力学性质仍然会影响细胞与 ECM 的相互作用。事实上,细胞-基底牵引力与摩擦系数呈双相关系,这个参数可用于量化粘着斑的性质。相比之下,细胞速度与该参数呈单调递减函数关系。此外,当最大细胞内应力从 400 增加到 600Pa 时,牵引力的增加幅度大于当基底硬度从 0.5 增加到 100kPa 时。这个数学模型能够量化粘着斑力学性质、细胞外硬度和细胞内应力对细胞与 ECM 相互作用的影响,应该有利于癌症发展的研究。