RECEPTOR-MEDIATED CELL ATTACHMENT AND DETACHMENT KINETICS .1. PROBABILISTIC MODEL AND ANALYSIS
RECEPTOR-MEDIATED CELL ATTACHMENT AND DETACHMENT KINETICS .1. PROBABILISTIC MODEL AND ANALYSIS
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DOI：
10.1016/s0006-3495(90)82430-9
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发表时间：
1990-10-01
影响因子：
3.4
通讯作者：
QUINN, JA
中科院分区：
文献类型：
--
作者：
COZENSROBERTS, C;LAUFFENBURGER, DA;QUINN, JA
受体介导的细胞与配体涂层表面的黏附动力学在许多生理和生物技术相关过程中起着关键作用。我们提出了一个细胞和表面之间受体-配位键形成的概率模型来描述在流体剪切场中黏附的可能性。我们的模型推广了Hammer和Lauffenburger(Hammer，D.A.和D.A.Lauffenburger)的确定性模型。1987年。BiPhys J.52：475-487)到一个概率框架，在这个框架中，我们计算细胞和表面之间在任何给定时间存在一定数量的键的概率。概率框架用于解释涉及相对较少反应分子的化学反应中固有的偏离理想的确定性行为。研究了两种情况：第一，在没有流体应力的情况下细胞附着；第二，在流体应力存在的情况下，细胞分离。在附着的情况下，我们考察了作为附着时间的函数的成键的期望方差；也为脱离的情况提供了一个初始条件。然后将重点放在脱离上，我们预测作为关键系统参数的函数的瞬时行为，例如分散的流体力，受体-配体亲和力和速率常数，以及受体和配体密度。我们比较了概率模型和确定性模型的预测，并展示了确定性方法如何产生一些不准确的结果：例如，对于时间上连续的细胞附着或分离，它可能低估了细胞附着所需的时间，它可能高估了给定作用力水平下细胞分离所需的时间，以及它可能高估了细胞分离所需的力。
The kinetics of receptor-mediated cell adhesion to a ligand-coated surface play a key role in many physiological and biotechnology-related processes. We present a probabilistic model of receptor-ligand bond formaton between a cell and surface to describe the probability of adhesion in a fluid shear field. Our model extends the deterministic model of Hammer and Lauffenburger (Hammer, D. A., and D. A. Lauffenburger. 1987. Biophys J. 52:475-487) to a probabilistic framework, in which we calculate the probability that a certain number of bonds between a cell and surface exists at any given time. The probabilistic framework is used to account for deviations from ideal, deterministic behavior, inherent in chemical reactions involving relatively small numbers of reacting molecules. Two situations are investigated: first, cell attachment in the absence of fluid stress; and, second, cell detachment in the presence of fluid stress. In the attachment case, we examine the expected variance in bond formation as a function of attachment time; also provides an initial condition for the detachment case. Focusing then on detachment, we predict transient behavior as a function of key system parameters, such as the distractive fluid force, the receptor-ligand bond affinity and rate constants, and the receptor and ligand densities. We compare the predictions of the probabilistic model with those of a deterministic model, and show how a deterministic approach can yield some inaccurate results; e.g., it cannot for temporally continuous cell attachment or detachment, it can underestimate the time needed for cell attachment, it can overestimate the time required for cell detachment for a given level of force, and it can overestimate the force necessary for cell detachment.