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Liposomes, Exosomes, and Virosomes: From Modeling Complex
Membrane Processes to Medical Diagnostics and Drug Delivery
Poster Abstracts
105
33-POS
Board 17
Lipid Influences on Peptide Insertion Across Bilayers
Alexander G. Karabadzhak
, John Deacon, Donald M. Engelman.
Yale University, New Haven, CT, USA.
The study of polypeptide insertion into biological membranes can enhance our understanding of
membrane protein stability and folding, and also has potential practical applications. pH Low
Insertion Peptides (pHLIPs) are a family of water soluble peptides that bind to membrane
surfaces in a mainly unstructured form. Acidic pH triggers them to fold into helices and insert as
transmembrane helices. Due to their pH dependent properties, pHLIPs can target acidic tissues
such as tumors. Here we present a study of pHLIPs' interaction with both natural and artificial
membrane bilayers designed to model the various lipid compositions of healthy and cancerous
cell membranes. We constructed liposomes with varied ratios of cholesterol, phosphatidylserine
lipids (PS), and saturated phospholipids to mimic the plasma membranes of cancer cells. We
employed biophysical methods: fluorescence, CD and a centrifugal separation assay to study
pHLIP’s association with different membranes at different conditions. Results show that lipid
composition, liposome size, and the buffer environment affect pHLIPs' partition/association with
membranes. As pHLIP-based tumor-targeting agents move towards the clinic, understanding the
influence of lipid composition on their membrane insertion activity is an important step in
navigating the complex biodiversity in cancer cell membranes. This work was supported by
National Institute of Health grant GM 073857