Unveiling growth and dynamics of liposomes by graphene liquid cell-transmission electron microscopy
Unveiling growth and dynamics of liposomes by graphene liquid cell-transmission electron microscopy
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DOI：
10.1039/d2nr06147c
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发表时间：
2023-02-10
期刊：
影响因子：
6.7
通讯作者：
Shahbazian-Yassar，Reza
中科院分区：
文献类型：
--
作者：
Jabbari，Vahid;Sawczyk，Michal;Shahbazian-Yassar，Reza
脂质体是生物技术和生物医学目的的模型系统，从靶向药物递送到现代疫苗研究。然而，脂质体的生长机制在很大程度上是未知的。在这项工作中，磷脂酰胆碱为基础的脂质体的形成和演变进行了研究，在实时的石墨烯液体细胞透射电子显微镜（GLC-TEM）。我们揭示了磷脂酰胆碱（PC）脂质体的生长，融合和变性的重要步骤。我们发现，最初复杂的脂质聚集体类似胶束开始形成。这些聚集体随机合并，同时捕获水并形成小的原脂质体。纳米级容器继续吸水，直到它们的膜变得凸起并且不含多余的磷脂，得到不同大小的稳定PC脂质体。在初始阶段，原脂质体以10-15 nm s-1的速率生长，随后其生长速率为2-5 nm s-1，这受到溶液中脂质可用性的限制。分子动力学（MD）模拟用于了解胶束簇的结构，它们的演化和合并。还发现脂质体通过脂质双层对接融合，随后形成半融合隔膜和融合孔开放。脂质体变性可以通过膜的初始结构不稳定和变形，随后是包封液体的泄漏来描述。该研究为基于脂质的分子组装体的形成和生长提供了新的见解，适用于广泛的两亲性分子。
Liposome is a model system for biotechnological and biomedical purposes spanning from targeted drug delivery to modern vaccine research. Yet, the growth mechanism of liposomes is largely unknown. In this work, the formation and evolution of phosphatidylcholine-based liposomes are studied in real-time by graphene liquid cell-transmission electron microscopy (GLC-TEM). We reveal important steps in the growth, fusion and denaturation of phosphatidylcholine (PC) liposomes. We show that initially complex lipid aggregates resembling micelles start to form. These aggregates randomly merge while capturing water and forming small proto-liposomes. The nanoscopic containers continue sucking water until their membrane becomes convex and free of redundant phospholipids, giving stabilized PC liposomes of different sizes. In the initial stage, proto-liposomes grow at a rate of 10–15 nm s−1, which is followed by their growth rate of 2–5 nm s−1, limited by the lipid availability in the solution. Molecular dynamics (MD) simulations are used to understand the structure of micellar clusters, their evolution, and merging. The liposomes are also found to fuse through lipid bilayers docking followed by the formation of a hemifusion diaphragm and fusion pore opening. The liposomes denaturation can be described by initial structural destabilization and deformation of the membrane followed by the leakage of the encapsulated liquid. This study offers new insights on the formation and growth of lipid-based molecular assemblies which is applicable to a wide range of amphiphilic molecules.