PULS Group, Institute for Theoretical Physics and Interdisciplinary Center for Nanostructured Films, Friedrich-Alexander-University Erlangen-Nürnberg, Cauerstrasse 3, 91058 Erlangen, Germany.
Key Laboratory of Mechanics on Disaster and Environment in Western China, Ministry of Education, College of Civil Engineering and Mechanics, Lanzhou University, Lanzhou 730000, China.
Int J Mol Sci. 2021 Apr 2;22(7):3699. doi: 10.3390/ijms22073699.
Cells interact with their environment by forming complex structures involving a multitude of proteins within assemblies in the plasma membrane. Despite the omnipresence of these assemblies, a number of questions about the correlations between the organisation of domains and the biomechanical properties of the involved proteins, namely their length, flexibility and affinity, as well as about the coupling to the elastic, fluctuating membrane, remain open. Here we address these issues by developing an effective Kinetic Monte Carlo simulation to model membrane adhesion. We apply this model to a typical experiment in which a cell binds to a functionalized solid supported bilayer and use two ligand-receptor pairs to study these couplings. We find that differences in affinity and length of proteins forming adhesive contacts result in several characteristic features in the calculated phase diagrams. One such feature is mixed states occurring even with proteins with length differences of 10 nm. Another feature are stable nanodomains with segregated proteins appearing on time scales of cell experiments, and for biologically relevant parameters. Furthermore, we show that macroscopic ring-like patterns can spontaneously form as a consequence of emergent protein fluxes. The capacity to form domains is captured by an order parameter that is founded on the virial coefficients for the membrane mediated interactions between bonds, which allow us to collapse all the data. These findings show that taking into account the role of the membrane allows us to recover a number of experimentally observed patterns. This is an important perspective in the context of explicit biological systems, which can now be studied in significant detail.
细胞通过在质膜中的组装体中形成涉及多种蛋白质的复杂结构来与环境相互作用。尽管这些组装体无处不在，但仍有许多问题涉及到结构域的组织与参与蛋白的生物力学特性（即其长度、柔韧性和亲和力）之间的相关性，以及与弹性、波动膜的耦合，这些问题仍然没有答案。在这里，我们通过开发一种有效的动力学蒙特卡罗模拟来解决这些问题，以模拟膜粘连。我们将此模型应用于一个典型的实验中，其中一个细胞与功能化的固体支撑双层结合，并使用两个配体-受体对来研究这些耦合。我们发现，形成粘附接触的蛋白质的亲和力和长度差异导致在计算相图中出现几个特征性特征。其中一个特征是即使在长度差异为 10nm 的蛋白质中也会出现混合状态。另一个特征是稳定的纳米域，其中分离的蛋白质会在细胞实验的时间尺度上出现，并且对于生物学相关参数也是如此。此外，我们表明，由于新兴的蛋白质通量，宏观的环形图案可以自发形成。形成域的能力由一个序参量捕获，该序参量基于膜介导的键之间相互作用的 Virial 系数，这使我们能够对所有数据进行简化。这些发现表明，考虑到膜的作用，可以使我们恢复许多实验观察到的模式。这在明确的生物系统的背景下是一个重要的视角，现在可以对其进行更详细的研究。
