Garzon Dasgupta Andrei K, Martyanov Alexey A, Filkova Aleksandra A, Panteleev Mikhail A, Sveshnikova Anastasia N
Faculty of Physics, Lomonosov Moscow State University, 1/2 Leninskie gory, 119991 Moscow, Russia.
National Medical Research Centеr of Pediatric Hematology, Oncology and Immunology named after Dmitry Rogachev, 1 Samory Mashela St, 117198 Moscow, Russia.
Life (Basel). 2020 Jun 26;10(6):97. doi: 10.3390/life10060097.
The process of clustering of plasma membrane receptors in response to their agonist is the first step in signal transduction. The rate of the clustering process and the size of the clusters determine further cell responses. Here we aim to demonstrate that a simple 2-differential equation mathematical model is capable of quantitative description of the kinetics of 2D or 3D cluster formation in various processes. Three mathematical models based on mass action kinetics were considered and compared with each other by their ability to describe experimental data on GPVI or CR3 receptor clustering (2D) and albumin or platelet aggregation (3D) in response to activation. The models were able to successfully describe experimental data without losing accuracy after switching between complex and simple models. However, additional restrictions on parameter values are required to match a single set of parameters for the given experimental data. The extended clustering model captured several properties of the kinetics of cluster formation, such as the existence of only three typical steady states for this system: unclustered receptors, receptor dimers, and clusters. Therefore, a simple kinetic mass-action-law-based model could be utilized to adequately describe clustering in response to activation both in 2D and in 3D.
质膜受体在其激动剂作用下发生聚集的过程是信号转导的第一步。聚集过程的速率和聚集体的大小决定了进一步的细胞反应。在这里，我们旨在证明一个简单的二维微分方程数学模型能够定量描述各种过程中二维或三维聚集体形成的动力学。我们考虑了基于质量作用动力学的三种数学模型，并通过它们描述GPVI或CR3受体聚集（二维）以及白蛋白或血小板聚集（三维）响应激活的实验数据的能力相互比较。这些模型能够在复杂模型和简单模型之间切换后成功描述实验数据且不损失准确性。然而，为了匹配给定实验数据的单一参数集，需要对参数值进行额外限制。扩展的聚集模型捕捉到了聚集体形成动力学的几个特性，例如该系统仅存在三种典型的稳态：未聚集的受体、受体二聚体和聚集体。因此，一个基于简单动力学质量作用定律的模型可用于充分描述二维和三维中响应激活的聚集过程。
