Fusion mechanisms of asymmetric lipid vesicles and membranes mimicking the cell wall and endosome

Communication and transfer of material between cells is a fundamental process in cell biology. Nature uses vesicles for such cell-to-cell communication in the form of extracellular vesicles (EVs). EVs are innately biocompatible and have huge potential in therapeutics and diagnostics, thanks in part to the fact that they possess many functionally relevant moieties including nucleic acid cargoes, proteins, and surface receptors, whose roles in EV activity and biodistribution have been well studied. However, less is known about the role of the lipids, although it is has been shown that EV populations have significantly different lipid distributions depending on cell line and biogenesis. The uptake of EVs and other lipid particles is widely accepted as varying across cell types. While this is in part due to surface markers, it is also due to the lipid composition. In my group we are developing vesicles with asymmetric distribution of lipids across the membrane, which mimic the lipid compositions found in EVs. These synthetic asymmetric vesicles will allow us to decouple the role of lipids in such biological processes. In this experiment, we will use DNA to tether these asymmetric vesicles to the surface of free-floating lipid bilayers representing lipid compositions of cell membranes and intracellular compartments, and study their fusion processes.

细胞间的物质交流与转运是细胞生物学的核心过程。自然界以细胞外囊泡（extracellular vesicles, EVs）的形式利用囊泡实现此类细胞间通讯。细胞外囊泡天生具备生物相容性，在治疗与诊断领域拥有巨大应用潜力，这在一定程度上得益于其携带有诸多功能相关的组分，包括核酸货物、蛋白质与表面受体——这些组分在囊泡活性与生物分布中的作用已得到充分研究。不过，学界对脂质所发挥的作用尚了解有限，尽管已有研究表明，不同细胞系与生物发生途径来源的细胞外囊泡群体，其脂质分布存在显著差异。细胞对细胞外囊泡及其他脂质颗粒的摄取能力因细胞类型而异，这一观点已被广泛认可。该差异一方面源于表面标志物的不同，另一方面则与脂质组成相关。本课题组正在研发一种膜两侧脂质分布不对称的囊泡，其脂质组成可模拟细胞外囊泡中的脂质构成。这类合成的不对称囊泡将帮助我们将脂质在这类生物学过程中的作用与其他因素解耦开来。在本实验中，我们将利用DNA将这些不对称囊泡锚定在自由漂浮的脂质双层膜表面——该双层膜可模拟细胞膜与细胞内区室的脂质组成，并研究二者的融合过程。