Quantitative analysis of molecular partition towards lipid membranes using surface plasmon resonance
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Understanding the interplay between molecules and lipid membranes is fundamental when studying
cellular and biotechnological phenomena. Partition between aqueous media and lipid membranes is
key 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 a
powerful technique for studying 1:1 stoichiometric interactions but has limited application to lipid
membrane partition data. We have developed and applied a novel mathematical model for SPR data
treatment that enables determination of kinetic and equilibrium partition constants. The method uses
two complementary fitting models for association and dissociation sensorgram data. The SPR partition
data obtained for the antibody fragment F63, the HIV fusion inhibitor enfuvirtide, and the endogenous
drug kyotorphin towards POPC membranes were compared against data from independent techniques.
The comprehensive kinetic and partition models were applied to the membrane interaction data of
HRC4, 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 1:1
stoichiometric ligand-receptor binding into a new and immense field of applications: the interaction of
solutes such as biomolecules and drugs with lipids