Polypeptoids are small protein-like molecules that self-assemble to form nanoparticles in solution. Polypeptoids can be synthesized with a high degree of precision and are entirely biocompatible, leading to significant potential uses in therapeutics and drug delivery. In such applications, the polypeptoid based drug carriers must effectively deliver the drug within the cell, thus requiring a detailed understanding of their interactions with cell membranes. This work seeks to engineer the interactions of specific polypeptoid systems with cell membranes using membrane models known as liposomes. These are small submicron particles in solution that contain an interior compartment with a cell-wall-like flexible external membrane. The investigators will experimentally study the formation and disruption of single and multi-layer liposomes to engineer a variety of systems to deliver drugs to cells in a targeted way. As part of this work, undergraduate and graduate students will be trained in the use of sophisticated experimental tools. In addition, the investigators are committed to outreach activities to K-12 students through hands-on demonstrations. A strong aspect of the outreach will be to expose process technology students in the New Orleans Community College system to the molecular aspects that drive chemical, petrochemical, and pharmaceutical operations.
The specific class of polypeptoids that will be developed in this work include the hydrophobically modified polypeptoids or HMPs, which interact with the lipid bilayers through hydrophobe insertion into the bilayers, and thus disrupt the bilayer to form HMP+lipid fragments or rafts. The remarkable aspect of the manifestation of the hydrophobic effect is the propensity of these HMP+lipid rafts to reattach onto intact liposomes to form additional layers. Preliminary experimental observations indicate that there is a sheet-like winding and assembly of these rafts onto liposomes leading to double and multiple layers on liposomes. The connectivity of hydrophobes in a polymeric amphiphile such as HMP brings about a high density of insertions leading to rupture of liposomes into perhaps intact bilayer fragments. The reattachment of fragments is also a previously unrecognized manifestation of the hydrophobic interaction. Thus, a fundamental study of this phenomenon will lead to control over building layers onto liposomes and therefore lead to the development of new classes of fully biocompatible polymer-lipid assemblies. The potential to build bilayers onto liposomes and erythrosomes using a designed connective polymeric amphiphile has significant technical implications. These concepts have relevance to the attachment of drug-containing lipid entities to cell membranes and to vesicle systems. The ability of HMPs to remodel liposomes is a novel aspect of multilayer self-assembly with significant applications to using liposomes as multiple drug carriers.
This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
