Batsilas Lazaros, Berezhkovskii Alexander M, Shvartsman Stanislav Y
Department of Chemical Engineering and Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey 08544, USA.
Biophys J. 2003 Dec;85(6):3659-65. doi: 10.1016/S0006-3495(03)74783-3.
Autocrine signaling systems are commonly studied under cell culture conditions. In a typical cell culture assay, a layer of liquid medium covers a random two-dimensional dispersion of cells, which secrete ligands. In a growing number of experiments, it is important to characterize the spatial range of autocrine and paracrine cell communication. Currently, the spatial distribution of diffusing signals can be analyzed only indirectly, from their effects on the intracellular signaling or physiological responses of autocrine cells. To directly characterize the spatial range of secreted ligands, we propose a stochastic model for autocrine cell cultures and analyze it using a combination of analytical and computational tools. The two main results derived within the framework of this model are 1), an expression for the fraction of autocrine trajectories, i.e., the probability for a ligand to be trapped by the same cell from which it has been secreted; and 2), an expression for the spatial distribution of trapping points of paracrine trajectories. We test these analytical results by stochastic simulations with efficient Brownian dynamics code and apply our model to analyze the spatial operation of autocrine epidermal growth factor receptor systems.
自分泌信号系统通常在细胞培养条件下进行研究。在典型的细胞培养实验中，一层液体培养基覆盖着随机二维分布的分泌配体的细胞。在越来越多的实验中，表征自分泌和旁分泌细胞通讯的空间范围很重要。目前，只能通过扩散信号对自分泌细胞的细胞内信号传导或生理反应的影响来间接分析其空间分布。为了直接表征分泌配体的空间范围，我们提出了一种自分泌细胞培养的随机模型，并使用分析和计算工具相结合的方法对其进行分析。在该模型框架内得出的两个主要结果是：1）自分泌轨迹分数的表达式，即配体被分泌它的同一细胞捕获的概率；2）旁分泌轨迹捕获点空间分布的表达式。我们使用高效的布朗动力学代码通过随机模拟来测试这些分析结果，并应用我们的模型来分析自分泌表皮生长因子受体系统的空间运作。
