Department of Physics and Randall Centre for Cell and Molecular Biophysics, King's College London, London, England, United Kingdom.
PLoS One. 2020 Feb 7;15(2):e0226825. doi: 10.1371/journal.pone.0226825. eCollection 2020.
Molecular clustering at the plasma membrane has long been identified as a key process and is associated with regulating signalling pathways across cell types. Recent advances in microscopy, in particular the rise of super-resolution, have allowed the experimental observation of nanoscale molecular clusters in the plasma membrane. However, modelling approaches capable of recapitulating these observations are in their infancy, partly because of the extremely complex array of biophysical factors which influence molecular distributions and dynamics in the plasma membrane. We propose here a highly abstracted approach: an agent-based model dedicated to the study of molecular aggregation at the plasma membrane. We show that when molecules are modelled as though they can act (diffuse) in a manner which is influenced by their molecular neighbourhood, many of the distributions observed in cells can be recapitulated, even though such sensing and response is not possible for real membrane molecules. As such, agent-based offers a unique platform which may lead to a new understanding of how molecular clustering in extremely complex molecular environments can be abstracted, simulated and interpreted using simple rules.
分子在质膜上的聚类一直被认为是一个关键过程，它与调节跨细胞类型的信号通路有关。近年来，显微镜技术的进步，特别是超分辨率技术的兴起，使得人们能够在质膜中观察到纳米尺度的分子簇。然而，能够再现这些观察结果的建模方法还处于起步阶段，部分原因是影响质膜中分子分布和动力学的生物物理因素极其复杂。在这里，我们提出了一种高度抽象的方法：一种基于代理的模型，专门用于研究质膜上的分子聚集。我们表明，当分子被建模为可以根据其分子环境进行（扩散）作用时，可以再现许多在细胞中观察到的分布，即使对于真实的膜分子来说，这种感应和响应是不可能的。因此，基于代理的方法提供了一个独特的平台，可能会导致对在极其复杂的分子环境中分子聚类如何通过简单规则进行抽象、模拟和解释有一个新的理解。
