Peptide Nano-Capsules with Lipid Vesicle like Characteristics

Abstract

In a recent publication (Gudlur et al., (2012) PLOS ONE, 7 (9) e45374), we described a nano-capsule made from the assembly of a mixture of two poly-cationic branched amphiphilic peptides bis(FLIVI)-K-K4 and bis(FLIVIGSII)-K-K4 that have a molecular architecture analogous to that of phospholipids. These peptides self-assemble in water to form hollow structures capable of trapping solutes. The ability of these peptides to assemble into bilayer-delimited spheres is a function of the unique nature of these peptide sequences - that reversibly transition from an alpha helical conformation in 2,2,2-Trifluoroethanol, to a beta sheet in water. These flexible capsules possess many of the properties of phospholipid vesicles such as fusion, solute encapsulation and an ability to be resized by membrane extrusion through polycarbonate filters with defined pore sizes. Here, we demonstrate the biophysical characteristics of these nano-capsules; including, their mode of assembly, the properties of the bilayer defined by the branched hydrophobic sequences, high thermodynamic stability, kinetics of fusion, and their ability to retain their cargo in cellular systems for an extended duration of time without any apparent degradation. The capsules can - like their lipid counterparts - not only be resized, but also maintained there at by reducing the temperature to 4° C, owing to what appears to be a temperature dependent conformational transformation. Moreover, these biomaterial constructs seem to retain their structural integrity even when subjected to alpha particle emissions. The versatility of these peptide nano-capsules lies in our ability to modify the individual peptide sequences with ligands and molecular markers; making these constructs potentially desirable as biocompatible vehicles for the targeted delivery of cargo into the cells.Biophysical Society Conference 2014.