Kuusela Esa, Alt Wolfgang
Department of Engineering Physics, Helsinki University of Technology, Otakaari 1, FI-02150, Espoo, Finland.
J Math Biol. 2009 Jan;58(1-2):135-61. doi: 10.1007/s00285-008-0179-x. Epub 2008 May 17.
The motility of cells crawling on a substratum has its origin in a thin cell organ called lamella. We present a 2-dimensional continuum model for the lamella dynamics of a slowly migrating cell, such as a human keratinocyte. The central components of the model are the dynamics of a viscous cytoskeleton capable to produce contractile and swelling stresses, and the formation of adhesive bonds in the plasma cell membrane between the lamella cytoskeleton and adhesion sites at the substratum. We will demonstrate that a simple mechanistic model, neglecting the complicated signaling pathways and regulation processes of a living cell, is able to capture the most prominent aspects of the lamella dynamics, such as quasi-periodic protrusions and retractions of the moving tip, retrograde flow of the cytoskeleton and the related accumulation of focal adhesion complexes in the leading edge of a migrating cell. The developed modeling framework consists of a nonlinearly coupled system of hyperbolic, parabolic and ordinary differential equations for the various molecular concentrations, two elliptic equations for cytoskeleton velocity and hydrodynamic pressure in a highly viscous two-phase flow, with appropriate boundary conditions including equalities and inequalities at the moving boundary. In order to analyse this hybrid continuum model by numerical simulations for different biophysical scenarios, we use suitable finite element and finite volume schemes on a fixed triangulation in combination with an adaptive level set method describing the free boundary dynamics.
细胞在基质上爬行的运动起源于一种名为片层的薄细胞器官。我们提出了一个二维连续介质模型,用于描述缓慢迁移细胞(如人类角质形成细胞)的片层动力学。该模型的核心组成部分包括:能够产生收缩应力和膨胀应力的粘性细胞骨架的动力学,以及片层细胞骨架与基质上粘附位点之间的质膜中粘附键的形成。我们将证明,一个简单的机械模型,忽略活细胞复杂的信号通路和调节过程,能够捕捉片层动力学的最显著方面,如移动尖端的准周期性突出和缩回、细胞骨架的逆行流动以及迁移细胞前沿粘着斑复合物的相关积累。所开发的建模框架由一个非线性耦合系统组成,该系统包含用于各种分子浓度的双曲型、抛物型和常微分方程,以及用于高粘性两相流中细胞骨架速度和流体动力压力的两个椭圆型方程,并带有适当的边界条件,包括移动边界处的等式和不等式。为了通过数值模拟分析不同生物物理场景下的这个混合连续介质模型,我们在固定三角剖分上使用合适的有限元和有限体积格式,并结合描述自由边界动力学的自适应水平集方法。