Biophysical Society Thematic Meeting

Liposomes, Exosomes, and Virosomes: From Modeling Complex

Membrane Processes to Medical Diagnostics and Drug Delivery

Poster Abstracts

7-POS

Board 4

Enhanced Functional Durability of Membrane Proteins in Hybrid Lipid-Block Copolymer

Vesicles

Sanobar Khan

, Mengqiu Li

, Lars Jeuken

Paul A. Beales

University of Leeds, Leeds, United Kingdom.

University of Leeds, Leeds, United Kingdom,

Membrane proteins make up approximately one third of all proteins and are the targets of around

60% of drugs currently on the market. Their broad range of functions from transmembrane

transport and signal transduction to adhesion and catalysis also makes membrane proteins

attractive constituents within novel bio-/nano- technologies. However membrane proteins are (in

general) difficult to handle and, when in reconstituted systems, tend to lack the long-term

stability that is often required for technological applications. With the aim of improving the

functional durability of reconstituted membrane proteins, we are investigating the use of hybrid

lipid-block copolymer vesicles. Hybrid vesicles have been reported to synergistically combine

the natural biocompatibility of phospholipid bilayers with the mechanical robustness and

stability of polymersome membranes. Using cytochrome

as a model protein, we demonstrate

that this membrane protein can be reconstituted into the membrane of hybrid vesicles. We find

that cytochrome

retains favourable activity when reconstituted in hybrid vesicles with

moderate polymer content compared to the activity in traditional proteoliposomes. The

advantage of hybrid vesicles over simple liposomes becomes evident from the long term stability

of membrane protein function: cytochrome

loses all functional activity in liposomes within

3-4 weeks, while significant (~50%) protein activity was retained within hybrid vesicle

formulations after >6 weeks. Therefore hybrid vesicles show great promise for durable

formulation of membrane proteins for applications that require extended functional lifetimes.