Law Everest, Li Yiwei, Kahraman Osman, Haselwandter Christoph A
Department of Physics and Astronomy and Department of Quantitative and Computational Biology, University of Southern California, Los Angeles, California 90089, USA.
Phys Rev E. 2021 Jul;104(1-1):014403. doi: 10.1103/PhysRevE.104.014403.
Synaptic receptor and scaffold molecules self-assemble into membrane protein domains, which play an important role in signal transmission across chemical synapses. Experiment and theory have shown that the formation of receptor-scaffold domains of the characteristic size observed in nerve cells can be understood from the receptor and scaffold reaction and diffusion processes suggested by experiments. We employ here kinetic Monte Carlo (KMC) simulations to explore the self-assembly of synaptic receptor-scaffold domains in a stochastic lattice model of receptor and scaffold reaction-diffusion dynamics. For reaction and diffusion rates within the ranges of values suggested by experiments we find, in agreement with previous mean-field calculations, self-assembly of receptor-scaffold domains of a size similar to that observed in experiments. Comparisons between the results of our KMC simulations and mean-field solutions suggest that the intrinsic noise associated with receptor and scaffold reaction and diffusion processes accelerates the self-assembly of receptor-scaffold domains, and confers increased robustness to domain formation. In agreement with experimental observations, our KMC simulations yield a prevalence of scaffolds over receptors in receptor-scaffold domains. Our KMC simulations show that receptor and scaffold reaction-diffusion dynamics can inherently give rise to plasticity in the overall properties of receptor-scaffold domains, which may be utilized by nerve cells to regulate the receptor number at chemical synapses.
突触受体和支架分子自组装成膜蛋白结构域，这在跨化学突触的信号传递中起着重要作用。实验和理论表明，从实验所提出的受体和支架反应及扩散过程可以理解在神经细胞中观察到的特征尺寸的受体 - 支架结构域的形成。我们在此采用动力学蒙特卡罗（KMC）模拟，在受体和支架反应 - 扩散动力学的随机晶格模型中探索突触受体 - 支架结构域的自组装。对于实验所建议的反应和扩散速率范围内的值，我们发现，与先前的平均场计算一致，形成了与实验中观察到的尺寸相似的受体 - 支架结构域。我们的KMC模拟结果与平均场解之间的比较表明，与受体和支架反应及扩散过程相关的内在噪声加速了受体 - 支架结构域的自组装，并赋予结构域形成更高的稳健性。与实验观察结果一致，我们的KMC模拟显示在受体 - 支架结构域中支架比受体更普遍。我们的KMC模拟表明，受体和支架反应 - 扩散动力学可以固有地导致受体 - 支架结构域整体性质的可塑性，神经细胞可能利用这一点来调节化学突触处的受体数量。
