Department of Chemistry, Boston University, 590 Commonwealth Avenue, Boston, Massachusetts 02215, United States.
Department of Physics, Boston University, 590 Commonwealth Avenue, Boston, Massachusetts 02215, United States.
J Phys Chem B. 2024 Mar 7;128(9):2087-2099. doi: 10.1021/acs.jpcb.3c08149. Epub 2024 Feb 26.
Intrinsically disordered peptides (IDPs) have been found to undergo liquid-liquid phase separation (LLPS) and produce complex coacervates that play numerous regulatory roles in the cell. Recent experimental studies have discovered that LLPS at or near the membrane surface helps in the biomolecular organization during signaling events and can significantly alter the membrane morphology. However, the molecular mechanism and microscopic details of such processes still remain unclear. Here we study the effect of polyampholyte and polyelectrolyte condensation on two different anionic membranes, as they represent a majority of naturally occurring IDPs. The polyampholytes are fifty-residue polymers, made of glutamate(E) and lysine(K) with different charge patterns. The polyelectrolytes are separate chains of and . We first calibrate the MARTINI v3.0 force field and then perform long-time-scale coarse-grained molecular dynamics simulations. We find that condensates formed by all the polyampholytes get adsorbed on the membrane. However, the strong polyampholytes (i.e., blocky sequences) can remodel the membranes more prominently than the weaker ones (i.e., scrambled sequences). Condensates formed by the blocky sequences induce a significant negative curvature (∼0.1 nm) and local demixing of lipids, whereas those by the scrambled sequences tend to wet the membrane to a greater extent without generating significant curvature or demixing. We perform several microscopic analyses to characterize the nature of the interaction between membranes and these condensates. Our analyses of interaction energetics reveal that membrane remodeling and/or wetting are favored by enhanced interactions between polyampholytes with lipids and the counterions.
无定形多肽 (IDPs) 已被发现会发生液-液相分离 (LLPS)，并产生复杂的凝聚物，在细胞中发挥多种调节作用。最近的实验研究发现，接近或在膜表面发生的 LLPS 有助于信号事件中的生物分子组织，并且可以显著改变膜形态。然而，这些过程的分子机制和微观细节仍然不清楚。在这里，我们研究了聚两性电解质和聚电解质缩合对两种不同阴离子膜的影响，因为它们代表了大多数天然存在的 IDPs。聚两性电解质是由谷氨酸 (E) 和赖氨酸 (K) 组成的 50 个残基聚合物，具有不同的电荷模式。聚电解质是 和 的单独链。我们首先校准 MARTINI v3.0 力场，然后进行长时间尺度的粗粒度分子动力学模拟。我们发现所有聚两性电解质形成的凝聚物都会被吸附在膜上。然而，强聚两性电解质（即块状序列）比弱聚两性电解质（即随机序列）更能显著重塑膜。由块状序列形成的凝聚物会引起显著的负曲率（约 0.1nm）和局部脂质去混合，而由随机序列形成的凝聚物则更倾向于在不产生显著曲率或去混合的情况下润湿膜。我们进行了几次微观分析来表征膜和这些凝聚物之间相互作用的性质。我们对相互作用能的分析表明，膜重塑和/或润湿更有利于聚两性电解质与脂质和抗衡离子之间增强的相互作用。
