Nuclear Magnetic Resonance Center, Institute of Organic Chemistry, Bulgarian Academy of Sciences, ulica Acad. G. Bonchev, blok 9, 1113 Sofia, Bulgaria.
Soft Matter. 2021 Mar 18;17(10):2753-2764. doi: 10.1039/d0sm01898h.
We carried out a series of coarse-grained molecular dynamics liposome-copolymer simulations with varying extent of copolymer concentration in an attempt to understand the effect of copolymer structure and concentration on vesicle self-assembly and stability. For one particular case molecular dynamics simulation data was successfully verified against experimental NMR results enhancing the credulity in the simulation methodology. The study focused on a new class of promising copolymers based on ethylene oxide (EO) chains and short blocks of aliphatic double chains that mimic lipid tails. The lipid mimetic units are based on 1,3-didodecyloxy-2-glycidylglycerol (DDGG) and 1,3-didodecyloxy-propane-2-ol (DDP). The conducted simulations indicate that multiple lipid anchor-bearing copolymers lead to stable hybrid liposome formations. Single lipid bearing might incur liposome-stabilizing potential for relatively small ethylene oxide chains but fails dramatically in combination with a longer EO-based moiety. The consistency of the theoretical evidence with experimental NMR observation for certain cases provides confidence for the relevance of the methodology in eliciting the factors governing liposome-polymer stability which is of fundamental and practical significance.
我们进行了一系列粗粒分子动力学脂质体-共聚物模拟，共聚物浓度变化，试图了解共聚物结构和浓度对囊泡自组装和稳定性的影响。对于一个特定的案例，分子动力学模拟数据成功地验证了实验 NMR 结果，提高了模拟方法的可信度。该研究集中于一类基于环氧乙烷（EO）链和短脂肪双链块的新型有前途的共聚物，这些共聚物模拟脂质尾部。脂质模拟单元基于 1,3-二(十二烷氧基)-2-缩水甘油基甘油（DDGG）和 1,3-二(十二烷氧基)-丙烷-2-醇（DDP）。进行的模拟表明，多个含脂质锚的共聚物导致稳定的混合脂质体形成。单一的脂质结合可能对相对较小的环氧乙烷链具有稳定脂质体的潜力，但与较长的基于 EO 的部分结合时会显著失败。在某些情况下，理论证据与实验 NMR 观察结果的一致性为该方法在引发影响脂质体-聚合物稳定性的因素方面的相关性提供了信心，这具有重要的理论和实际意义。
