Hammer D A, Lauffenburger D A
Department of Chemical Engineering, University of Pennsylvania, Philadelphia 19104.
Biophys J. 1987 Sep;52(3):475-87. doi: 10.1016/S0006-3495(87)83236-8.
We present a dynamical model for receptor-mediated adhesion of cells in a shear field of viscous fluid to surfaces coated with ligand molecules complementary to receptors in the cell membrane. We refer to this model as the "point attachment model" because it considers the contact area between the cell and the surface to be a small, homogeneous region that mediates the initial attachment of the cell to the surface. Using a phase plane analysis of a system of nonlinear ordinary differential equations which govern the changes in free receptor density and bond density within the contact area with time, we can predict the conditions for which adhesion between the cell and the surface will take place. Whether adhesion occurs depends on values of dimensionless quantities that characterize the interaction of the cell and its receptors with the surface and its ligand, such as the bond formation rate, the receptor-ligand affinity, the fluid mechanical force, the receptor mobility, and the contact area. A key result is that there are two regimes in which different chemical and physical forces dominate: a rate-controlled high affinity regime and an affinity-controlled low-affinity regime. Many experimental observations can be explained by understanding which of these regimes is appropriate. We also provide simple approximate analytical solutions, relating adhesiveness to cell and surface properties as well as fluid forces, which allow convenient testing of model predictions by experiment.
我们提出了一个动力学模型,用于描述在粘性流体剪切场中,细胞通过受体介导与涂有与细胞膜受体互补的配体分子的表面发生粘附的过程。我们将此模型称为“点附着模型”,因为它将细胞与表面之间的接触区域视为一个小的、均匀的区域,该区域介导细胞与表面的初始附着。通过对一个非线性常微分方程组进行相平面分析,该方程组描述了接触区域内自由受体密度和键密度随时间的变化,我们可以预测细胞与表面发生粘附的条件。粘附是否发生取决于一些无量纲量的值,这些量表征了细胞及其受体与表面及其配体之间的相互作用,例如键形成速率、受体 - 配体亲和力、流体机械力、受体迁移率和接触面积。一个关键结果是存在两种不同的化学和物理力主导的状态:速率控制的高亲和力状态和亲和力控制的低亲和力状态。通过理解哪种状态适用,可以解释许多实验观察结果。我们还提供了简单的近似解析解,将粘附性与细胞和表面特性以及流体力联系起来,这使得通过实验方便地测试模型预测成为可能。