title: Amphiphilic Polypeptoids Serve as the Connective Glue to Transform Liposomes into Multilamellar Structures with Closely Spaced Bilayers.
abstract: We report the ability of hydrophobically modified polypeptoids (HMPs), which are amphiphilic pseudopeptidic macromolecules, to connect across lipid bilayers and thus form layered structures on liposomes. The HMPs are obtained by attaching hydrophobic decyl groups at random points along the polypeptoid backbone. Although native polypeptoids (with no hydrophobes) have no effect on liposomal structure, the HMPs remodel the unilamellar liposomes into structures with comparable diameters but with multiple concentric bilayers. The transition from single-bilayer to multiple-bilayer structures is revealed by small-angle neutron scattering (SANS) and cryo-transmission electron microscopy (cryo-TEM). The spacing between bilayers is found to be relatively uniform at ∼6.7 nm. We suggest that the amphiphilic nature of the HMPs explains the formation of multibilayered liposomes; i.e., the HMPs insert their hydrophobic tails into adjacent bilayers and thereby serve as the connective glue between bilayers. At higher HMP concentrations, the liposomes are entirely disrupted into much smaller micellelike structures through extensive hydrophobe insertion. Interestingly, these small structures can reattach to fresh unilamellar liposomes and self-assemble to form new two-bilayer liposomes. The two-bilayer liposomes in our study are reminiscent of two-bilayer organelles such as the nucleus in eukaryotic cells. The observations have significance in designing new nanoscale drug delivery carriers with multiple drugs on separate lipid bilayers and extending liposome circulation times with entirely biocompatible materials.
authors.forename: Yueheng
authors.initials: Y
authors.lastname: Zhang
authors.forename: Sunting
authors.initials: S
authors.lastname: Xuan
authors.forename: Olasehinde
authors.initials: O
authors.lastname: Owoseni
authors.forename: Marzhana
authors.initials: M
authors.lastname: Omarova
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.forename: Michelle E
authors.initials: ME
authors.lastname: Saito
authors.forename: Jibao
authors.initials: J
authors.lastname: He
authors.forename: Gary L
authors.initials: GL
authors.lastname: McPherson
authors.affiliation: Department of Chemical and Biomolecular Engineering, University of Maryland , College Park, Maryland 20742, United States.
authors.forename: Srinivasa R
authors.initials: SR
authors.lastname: Raghavan
authors.forename: Donghui
authors.identifier: 0000-0003-0779-6438
authors.initials: D
authors.lastname: Zhang
authors.forename: Vijay T
authors.identifier: 0000-0001-5426-7585
authors.initials: VT
authors.lastname: John
mesh_terms: D020285:Cryoelectron Microscopy; D057927:Hydrophobic and Hydrophilic Interactions; D008051:Lipid Bilayers / Q000737:chemistry*; D008081:Liposomes / Q000737:chemistry*; D046529:Microscopy, Electron, Transmission; D010713:Phosphatidylcholines / Q000737:chemistry*; D053835:Unilamellar Liposomes / Q000737:chemistry*
chemical_list: D008051:Lipid Bilayers; D008081:Liposomes; D010713:Phosphatidylcholines; D053835:Unilamellar Liposomes