Omarova Marzhana, Zhang Yueheng, Mkam Tsengam Igor Kevin, He Jibao, Yu Tianyi, Zhang Donghui, John Vijay
Department of Chemical and Biomolecular Engineering, Tulane University, New Orleans, Louisiana 70118, United States.
Department of Chemistry, Louisiana State University, Baton Rouge, Louisiana 70803, United States.
J Phys Chem B. 2021 Apr 1;125(12):3145-3152. doi: 10.1021/acs.jpcb.0c11477. Epub 2021 Mar 17.
The hydrophobic effect of alkyl group insertion into phospholipid bilayers is exploited in modifying and modulating vesicle structure. We show that amphiphilic polypeptoids (peptide mimics) with -decyl side chains, which we term as hydrophobe-containing polypeptoids (HCPs), can insert the alkyl hydrophobes into the membrane bilayer of phospholipid-based vesicles. Such insertion leads to disruption of the liposomes and the formation of HCP-lipid complexes that are colloidally stable in aqueous solution. Interestingly, when these complexes are added to fresh liposomes, remnant uncomplexed hydrophobes (the -decyl groups) bridge liposomes and fuse them. The fusion leads to the engulfing of liposomes and the formation of multilayered vesicles. The morphology of the liposome system can be changed from stopping fusion and forming clustered vesicles to the continued formation of multilayered liposomes simply by controlling the amount of the HCP-lipid complex added. The entire procedure occurs in aqueous systems without the addition of any other solvents. There are several implications to these observations including the biological relevance of mimicking fusogenic proteins such as the SNARE proteins and the development of new drug delivery technologies to impact delivery to cell organelles.
烷基插入磷脂双层膜的疏水效应被用于修饰和调节囊泡结构。我们发现，带有癸基侧链的两亲性类肽（肽模拟物），我们将其称为含疏水基团类肽（HCPs），能够将烷基疏水基团插入基于磷脂的囊泡膜双层中。这种插入导致脂质体破裂并形成在水溶液中具有胶体稳定性的HCP - 脂质复合物。有趣的是，当将这些复合物添加到新鲜脂质体中时，残余的未复合疏水基团（癸基）会桥接脂质体并使其融合。这种融合导致脂质体被吞噬并形成多层囊泡。通过简单地控制添加的HCP - 脂质复合物的量，脂质体系统的形态可以从阻止融合并形成聚集囊泡转变为持续形成多层脂质体。整个过程在水性系统中进行，无需添加任何其他溶剂。这些观察结果有几个意义，包括模拟诸如SNARE蛋白等融合蛋白的生物学相关性以及开发影响向细胞器递送的新药物递送技术。
