DUGi

Quantitative analysis of molecular partition towards lipid membranes using surface plasmon resonance

http://dugi.udg.edu/item/http:@@@@hdl.handle.net@@2072@@289384

Understanding the interplay between molecules and lipid membranes is fundamental when studyingcellular and biotechnological phenomena. Partition between aqueous media and lipid membranes iskey to the mechanism of action of many biomolecules and drugs. Quantifying membrane partition,through adequate and robust parameters, is thus essential. Surface Plasmon Resonance (SPR) is apowerful technique for studying 1:1 stoichiometric interactions but has limited application to lipidmembrane partition data. We have developed and applied a novel mathematical model for SPR datatreatment that enables determination of kinetic and equilibrium partition constants. The method usestwo complementary fitting models for association and dissociation sensorgram data. The SPR partitiondata obtained for the antibody fragment F63, the HIV fusion inhibitor enfuvirtide, and the endogenousdrug kyotorphin towards POPC membranes were compared against data from independent techniques.The comprehensive kinetic and partition models were applied to the membrane interaction data ofHRC4, a measles virus entry inhibitor peptide, revealing its increased affinity for, and retention in,cholesterol-rich membranes. Overall, our work extends the application of SPR beyond the realm of 1:1stoichiometric ligand-receptor binding into a new and immense field of applications: the interaction ofsolutes such as biomolecules and drugs with lipids

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