Lipodendrisomes: Co-assembly of New Comb-Rod Dendritic Block Copolymers with Lipids for Tailored Functional Vesicles

Massachusetts Institute Of Technology, Cambridge MA

Investigators

Abstract

TECHNICAL SUMMARY: A newly designed series of linear-dendritic comb-rod copolymers consisting of a rigid alkyl substituted helical polypeptide block and a neutral hydrophilic polyester dendritic block will be designed and synthesized to create novel amphiphiles with constrained architectures. When these alkyl-peptide dendritic block copolymers co-assemble with phospholipids, new functional vesicles, or lipodendrisomes, will be generated which present regions of localized functional density on the surfaces of lipid membranes or exhibit regular shapes for which localized function may be distributed at defects or edges of the vesicle. Furthermore, the relative length of the alkyl chains and linear peptide block, as well as the dendrimer generation, will be used to tune the presentation and arrangement of functional dendritic structures within or without the lipid membrane. It is the objective and intellectual merit of this work to undertake the first systematic and inclusive examination of comb-rod dendritic block copolymer self-assembly with lipids in the solution state, and the investigation of the stabilized nanoparticles resulting from this assembly. The potential to create controlled nanostructures that span the membrane of the block copolymer via functionalization and manipulation of molecular parameters of the block copolymer could lead to the design of polymers with function that mimic transmembrane proteins, allowing the regulation or gating of hydrophilic materials such as ions, small molecules or proteins across dendritic-functionalized isolated pores. The capability of generating ordered, phase segregated or clustered surface groups that present high numbers of specific functional groups on the surface could yield highly effectual targeted polyvalent drug delivery systems. Furthermore, the unique asymmetric nature of the alkyl-peptide backbone and dendritic head group appear to create defects in liposomes that may result in faceted or irregular shapes or vesicle morphologies; the orientation and localization of the block copolymer in such systems will be studied extensively. The potential design of block copolymer lipodendrisomes that exhibit functionality in specific regions of the vesicle will be examined for three dimensional self-assembly of the unique polygonal structures, as well as functionalization to create unique nanostructures for a range of applications from orientational fluidic and surface assembly to sensing nanoparticles and biological and biomedical systems with specific cellular interactions. Finally, the ability to reversibly or irreversibly induce the spontaneous formation of functionalized gates, ligands or proteins on membrane surfaces with photo- or thermo-responsive groups will be examined. NON-TECHNICAL SUMMARY: Self-assembling polymers consisting linear and highly branched dendritic segments will be designed to undergo self-assembly in solution with naturally occurring lipid molecules. The resulting structures are anticipated to introduce unique functionality to traditional liposomes by presenting specific desired groups to the surface of the liposome to generate nanoscale clusters of protein, ligand or inorganic nanoparticles, or by creating unique channels in the liposomes that mimic the ion channels and proteins in cell membranes. A greater understanding of how these designed elements behave in liposomal systems could lead to design principles guiding the development of artificial transmembrane proteins or membrane-active surface elements. These systems may yield new materials systems for the delivery of drugs or proteins, ions, or small molecules across the membrane or the manipulation of cell receptors at surfaces. The research described here is an integral part of the investigator's research and teaching plan, and includes the education and training of undergraduate and graduate students in the laboratory environment, the integration of concepts of self-assembly in the teaching of polymer science in undergraduate and graduate courses. The mentorship of students takes place on every level, including academic and career issues, work and family concerns, and includes a number of women and minority students. Outreach of the PI includes her involvement in the MIT Summer Research Program to encourage underrepresented minority undergraduates to attend graduate school, and the participation in a high school teacher exchange program to expose teachers to research and new concepts to teach in the polymer science and colloid science areas.