Racah Institute of Physics, The Hebrew University, Jerusalem, Israel.
Front Immunol. 2018 Sep 11;9:2051. doi: 10.3389/fimmu.2018.02051. eCollection 2018.
Molecular interactions across intercellular interfaces serve to convey information between cells and to trigger appropriate cell functions. Examples include cell development and growth in tissues, neuronal and immune synapses (ISs). Here, we introduce an agent-based Monte-Carlo simulation of user-defined cellular interfaces. The simulation allows for membrane molecules, embedded at intercellular contacts, to diffuse and interact, while capturing the topography and energetics of the plasma membranes of the interface. We provide a detailed example related to pattern formation in the early IS. Using simulation predictions and three-color single molecule localization microscopy (SMLM), we detected the intricate mutual patterning of T cell antigen receptors (TCRs), integrins and glycoproteins in early T cell contacts with stimulating coverslips. The simulation further captures the dynamics of the patterning under the experimental conditions and at the IS with antigen presenting cells (APCs). Thus, we provide a generic tool for simulating realistic cell-cell interfaces, which can be used for critical hypothesis testing and experimental design in an iterative manner.
细胞间界面的分子相互作用有助于在细胞之间传递信息，并触发适当的细胞功能。例如，组织中的细胞发育和生长、神经元和免疫突触 (IS)。在这里，我们引入了一种基于代理的蒙特卡罗模拟用户定义的细胞界面。该模拟允许嵌入在细胞间接触处的膜分子扩散和相互作用，同时捕获界面的质膜的形貌和能量学。我们提供了一个与早期 IS 中模式形成相关的详细示例。使用模拟预测和三色单分子定位显微镜 (SMLM)，我们检测到在刺激盖玻片上 T 细胞与 APC 早期接触时，T 细胞受体 (TCR)、整合素和糖蛋白之间复杂的相互图案化。该模拟进一步捕捉了在实验条件下和在具有抗原呈递细胞 (APC) 的 IS 下图案形成的动力学。因此，我们提供了一种用于模拟现实细胞-细胞界面的通用工具，可用于以迭代方式进行关键假设检验和实验设计。
