Lazopoulos Konstantinos A, Stamenović Dimitrije
Mechanics Laboratory, Faculty of Applied Sciences, National Technical University of Athens, Athens, Greece.
J Biomech. 2008;41(6):1289-94. doi: 10.1016/j.jbiomech.2008.01.008. Epub 2008 Mar 4.
It is well documented that directed motion of cells is influenced by substrate stiffness. When cells are cultured on a substrate of graded stiffness, they tend to move from softer to stiffer regions--a process known as durotaxis. In this study, we propose a mathematical model of durotaxis described as an elastic stability phenomenon. We model the cytoskeleton (CSK) as a planar system of prestressed elastic line elements representing actin stress fibers (SFs), which are anchored via focal adhesions (FAs) at their end points to an elastic substrate of variable stiffness. The prestress in the SFs exerts a pulling force on FAs reducing thereby their chemical potential. Using Maxwell's global stability criterion, we obtain that the model stability increases as it is moved from a softer towards a stiffer region of the substrate. Numerical simulations reveal that elastic stability of SFs has a predominantly stabilizing effect, greater than the stabilizing effect of decreasing chemical potential of FAs. This is a novel finding which indicates that elasticity of the CSK plays an important role in cell migration and mechanosensing in general.
细胞的定向运动受底物硬度影响,这一点已有充分记录。当细胞在具有梯度硬度的底物上培养时,它们倾向于从较软区域向较硬区域移动——这一过程称为趋硬性。在本研究中,我们提出了一个将趋硬性描述为弹性稳定现象的数学模型。我们将细胞骨架(CSK)建模为一个平面系统,该系统由预应力弹性线元素组成,代表肌动蛋白应力纤维(SFs),它们通过粘着斑(FAs)在其端点锚定到可变硬度的弹性底物上。SFs中的预应力对FAs施加拉力,从而降低其化学势。使用麦克斯韦全局稳定性准则,我们得出当模型从底物的较软区域移向较硬区域时,其稳定性会增加。数值模拟表明,SFs的弹性稳定性具有主要的稳定作用,大于FAs化学势降低的稳定作用。这是一个新发现,表明CSK的弹性在一般的细胞迁移和机械传感中起着重要作用。