Biophysical Society Thematic Meeting | Ascona, Switzerland

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 1 , Mengqiu Li 2 , Lars Jeuken 2 , Paul A. Beales 1 . 2 University of Leeds, Leeds, United Kingdom. 1 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 bo 3 as a model protein, we demonstrate that this membrane protein can be reconstituted into the membrane of hybrid vesicles. We find that cytochrome bo 3 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 bo 3 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.

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