Biophysical Society Thematic Meeting | Ascona, Switzerland

Liposomes, Exosomes, and Virosomes: From Modeling Complex Membrane Processes to Medical Diagnostics and Drug Delivery

Poster Abstracts

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

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