A STOCHASTIC-MODEL FOR ADHESION-MEDIATED CELL RANDOM MOTILITY AND HAPTOTAXIS
A STOCHASTIC-MODEL FOR ADHESION-MEDIATED CELL RANDOM MOTILITY AND HAPTOTAXIS
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DOI：
10.1007/bf00161199
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发表时间：
1993-07-01
影响因子：
1.9
通讯作者：
TRANQUILLO, RT
中科院分区：
文献类型：
--
作者：
DICKINSON, RB;TRANQUILLO, RT
血液和组织细胞的主动迁移在许多生理过程中都很重要，包括炎症、伤口愈合、胚胎发生和肿瘤细胞转移。这些细胞通过膜受体传递细胞质力来移动，膜受体与周围基质中的粘附配体特异性结合。近年来，许多研究集中在细胞外基质的组成及其成分的分布对细胞迁移速度和方向的影响。人们普遍认为，粘附的大小影响细胞速度和/或随机转动行为，而粘附梯度可能会偏置细胞运动的净方向，这种现象称为趋触性。目前尚不清楚这些反应背后的机制。提出了随机模型，以提供对基质中粘附配体的大小和分布如何影响细胞运动的机制理解。受体介导的细胞迁移被建模为不同时间尺度上随机过程的相互关系。粘附受体经历快速结合和运输，导致结合受体的随机空间分布在某个平均分布附近波动。这会导致细胞上的力的时空模式发生波动，进而在较长的时间尺度上影响速度和转动行为。模型方程是非线性随机微分方程 (SDE) 系统，它控制结合和游离受体的空间分布的时间演化以及细胞的方向和位置。这些 SDE 进行数值积分，以模拟模型细胞在均匀基质和粘附配体浓度梯度上的行为。此外，对控制 SDE 系统和相应的 Fokker-Planck 方程 (FPE) 的分析产生了指数的分析表达式，这些指数在细胞力学、形态学以及受体结合和运输参数方面表征了多个时间尺度上的细胞运动。对于均匀的粘附配体浓度，该分析提供了传统细胞运动指数的表达式，例如平均速度、方向持续时间和随机运动系数。在小梯度粘附中，FPE 的扰动分析产生了组成型细胞通量表达式，其中包括用于趋触定向细胞迁移的漂移项。触觉漂移包含被确定为方向偏差（滑行）、运动和正交的贡献的术语，其中滑行似乎在给定模型参数估计的情况下占主导地位。
The active migration of blood and tissue cells is important in a number of physiological processes including inflammation, wound healing, embryogenesis, and tumor cell metastasis. These cells move by transmitting cytoplasmic force through membrane receptors which are bound specifically to adhesion ligands in the surrounding substratum. Recently, much research has focused on the influence of the composition of extracellular matrix and the distribution of its components on the speed and direction of cell migration. It is commonly believed that the magnitude of the adhesion influences cell speed and/or random turning behavior, whereas a gradient of adhesion may bias the net direction of the cell movement, a phenomenon known as haptotaxis. The mechanisms underlying these responses are presently not understood.A stochastic model is presented to provide a mechanistic understanding of how the magnitude and distribution of adhesion ligands in the substratum influence cell movement. The receptor-mediated cell migration is modeled as an interrelation of random processes on distinct time scales. Adhesion receptors undergo rapid binding and transport, resulting in a stochastic spatial distribution of bound receptors fluctuating about some mean distribution. This results in a fluctuating spatio-temporal pattern of forces on the cell, which in turn affects the speed and turning behavior on a longer time scale. The model equations are a system of nonlinear stochastic differential equations (SDE's) which govern the time evolution of the spatial distribution of bound and free receptors, and the orientation and position of the cell. These SDE's are integrated numerically to simulate the behavior of the model cell on both a uniform substratum, and on a gradient of adhesion ligand concentration.Furthermore, analysis of the governing SDE system and corresponding Fokker-Planck equation (FPE) yields analytical expressions for indices which characterize cell movement on multiple time scales in terms of cell cytomechanical, morphological, and receptor binding and transport parameters. For a uniform adhesion ligand concentration, this analysis provides expressions for traditional cell movement indices such as mean speed, directional persistence time, and random motility coefficient. In a small gradient of adhesion, a perturbation analysis of the FPE yields a constitutive cell flux expression which includes a drift term for haptotactic directional cell migration. The haptotactic drift contains terms identified as contributions from directional orientation bias (taxis), kinesis, and orthotaxis, of which taxis appears to be predominant given estimates of the model parameters.