Candiolo Cancer Institute, FPO-IRCCS, Strada Provinciale 142, km 3.95, 10060 Candiolo, Italy.
Institute of Condensed Matter Physics and Complex Systems, Department of Applied Science and Technology, Politecnico di Torino, Corso Duca degli Abruzzi 24, 10129 Turin, Italy.
Phys Rev E. 2023 Aug;108(2-1):024401. doi: 10.1103/PhysRevE.108.024401.
Eukaryotic cells maintain their inner order by a hectic process of sorting and distillation of molecular factors taking place on their lipid membranes. A similar sorting process is implied in the assembly and budding of enveloped viruses. To understand the properties of this molecular sorting process, we have recently proposed a physical model [Zamparo et al., Phys. Rev. Lett. 126, 088101 (2021)]10.1103/PhysRevLett.126.088101, based on (1) the phase separation of a single, initially dispersed molecular species into spatially localized sorting domains on the lipid membrane and (2) domain-induced membrane bending leading to the nucleation of submicrometric lipid vesicles, naturally enriched in the molecules of the engulfed sorting domain. The analysis of the model showed the existence of an optimal region of parameter space where sorting is most efficient. Here the model is extended to account for the simultaneous distillation of a pool of distinct molecular species. We find that the mean time spent by sorted molecules on the membrane increases with the heterogeneity of the pool (i.e., the number of distinct molecular species sorted) according to a simple scaling law, and that a large number of distinct molecular species can in principle be sorted in parallel on cell membranes without significantly interfering with each other. Moreover, sorting is found to be most efficient when the distinct molecular species have comparable homotypic affinities. We also consider how valence (i.e., the average number of interacting neighbors of a molecule in a sorting domain) affects the sorting process, finding that higher-valence molecules can be sorted with greater efficiency than lower-valence molecules.
真核细胞通过脂质膜上发生的分子因子的分类和蒸馏这一繁忙过程来维持其内部秩序。类似的分类过程也存在于包膜病毒的组装和出芽过程中。为了理解这种分子分类过程的性质，我们最近提出了一个物理模型[Zamparo 等人，Phys. Rev. Lett. 126, 088101 (2021)]，该模型基于 (1) 单个最初分散的分子物种在脂质膜上的空间局部分类域的相分离，以及 (2) 导致亚微米脂质泡形成的域诱导膜弯曲，这些泡自然富含被包裹的分类域中的分子。模型分析表明，在参数空间的一个最优区域中，分类效率最高。在此基础上，该模型扩展到可以同时对一组不同的分子物种进行蒸馏。我们发现，分类分子在膜上的平均停留时间随着池（即，被分类的不同分子物种的数量）的异质性的增加而增加，根据一个简单的比例定律，并且原则上可以在细胞膜上并行对大量不同的分子物种进行分类，而不会彼此显著干扰。此外，当不同的分子物种具有可比的同型亲和力时，分类被发现是最有效的。我们还考虑了价数（即，在一个分类域中一个分子的相互作用邻居的平均数量）如何影响分类过程，发现高价数的分子可以比低价数的分子更有效地进行分类。
