A mathematical model of the coupled mechanisms of cell adhesion, contraction and spreading.

A mathematical model of the coupled mechanisms of cell adhesion, contraction and spreading.
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DOI:
10.1007/s00285-013-0656-8
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发表时间:
2014-03
影响因子:
1.9
通讯作者:
Farsad, Mehdi
Farsad, Mehdi
中科院分区:
数学4区
文献类型:
--
作者:
Vernerey, Franck J.;Farsad, Mehdi

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最近的研究表明,细胞伸展高度依赖于其细胞骨架的收缩性和其所处环境的力学性质。这种过程的动力学对于组织工程策略的发展至关重要,但也是伤口收缩、组织维持和血管生成的关键因素。为了更好地理解这种现象的基本物理学,本文描述了一个数学公式的细胞伸展和收缩,耦合的过程中的应力纤维的形成,突起生长通过肌动蛋白聚合在细胞边缘和动力学的跨膜蛋白(整合素),使细胞基质附着。进化中的细胞骨架被建模为流体、蛋白质和细丝的混合物,它们可以交换质量并产生收缩。特别是,除了自组装成应力纤维外,肌动蛋白单体还能够在细胞边界处嵌入肌动蛋白网络,以推动膜向前并产生突起。这些过程是可能的,通过发展的细胞基质附着复合物,从膜蛋白,称为整合素的机械敏感性平衡产生。在推导出驱动细胞演化和扩散动力学的控制方程后,我们引入了基于扩展有限元方法的数值解,并结合水平集公式。数值模拟表明,所提出的模型是能够捕获的依赖性细胞的扩展和收缩基板的刚度和化学。模型预测和实验观察之间的非常好的协议表明,力学起着很大的作用到耦合机制的收缩,粘附和扩展的粘附细胞。
Recent research has shown that cell spreading is highly dependent on the contractililty of its cytoskeleton and the mechanical properties of the environment it is located in. The dynamics of such process is critical for the development of tissue engineering strategy but is also a key player in wound contraction, tissue maintenance and angiogenesis. To better understand the underlying physics of such phenomena, the paper describes a mathematical formulation of cell spreading and contraction that couples the processes of stress fiber formation, protrusion growth through actin polymerization at the cell edge and dynamics of cross-membrane protein (integrins) enabling cell-substrate attachment. The evolving cell’s cytoskeleton is modeled as a mixture of fluid, proteins and filaments that can exchange mass and generate contraction. In particular, besides self-assembling into stress fibers, actin monomers able to polymerize into an actin meshwork at the cell’s boundary in order to push the membrane forward and generate protrusion. These processes are possible via the development of cell-substrate attachment complexes that arise from the mechano-sensitive equilibrium of membrane proteins, known as integrins. After deriving the governing equation driving the dynamics of cell evolution and spreading, we introduce a numerical solution based on the extended finite element method, combined with a level set formulation. Numerical simulations show that the proposed model is able to capture the dependency of cell spreading and contraction on substrate stiffness and chemistry. The very good agreement between model predictions and experimental observations suggests that mechanics plays a strong role into the coupled mechanisms of contraction, adhesion and spreading of adherent cells.
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