Aggregation, Fusion, and Leakage of Liposomes Induced by Peptides

Biological membranes are heterogeneous systems. Their functions are closely related to the lipid lateral segregation in the presence of membrane proteins. In this work, we designed two peptides, amphiphilic cationic peptides K3L8K3 and nonamphiphilic peptides K-20, and studied their interactions with binary liposomes in different phases (L-omega L-beta', and L-alpha/L-beta'). As mimics of membrane proteins, both K3L8K3 and K-20 can cause the liposomes to aggregate, fuse, or leak. These processes were closely related to the phases of liposomes. For the liposomes in L-alpha phase, heavy aggregation, fusion, and leakage were observed in the presence of either K-20 or K3L8K3. For the liposomes in L-beta' phase, neither K3L8K3 nor K-20 can induce fusion or leakage. For the liposomes in L-alpha/L-beta' phase, K3L8K3 caused the liposomes to aggregate, fuse, and leak, while K-20 only led to aggregation. The kinetics of aggregation, fusion, and leakage in each phase were recorded, and they were related to the lipid demixing in the presence of the peptide. Our work not only gained insight into the effect of the lipid demixing on the interactions between peptide and membrane, but also helped in developing drug delivery vehicles with liposomes as the platform.