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Methanol Accelerates DMPC Flip-Flop and Transfer: A SANS Study on Lipid Dynamics



Michael H. L. Nguyen, Mitchell DiPasquale, Brett W. Rickeard, Christopher B. Stanley, Elizabeth Kelley, Drew Marquardt


Methanol is a common solubilizing agent used for the study of transmembrane proteins/peptides in biological and synthetic membranes. Using small angle neutron scattering (SANS) and a strategic contrast matching scheme, we show that methanol has a unique impact on lipid dynamics. Under increasing methanol concentrations, isotopically-distinct 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) large unilamellar vesicle (LUV) populations exhibit increased mixing and scrambling rates. The lipid transfer and flip-flop rates display linear and exponential rate enhancements, respectively. Methanol, as a delivery vehicle of external agents in proteolipidic studies, is seen to influence the structural-functional relationship of bilayer composition, ultimately leading to a rapid loss of lipid asymmetry. A consequence of external delivery, despite better simulating some biological conditions (e.g. antimicrobial attack), is that researchers can misconstrue this lipid scrambling as an action of the proteins or peptides instead of the carrier solvents used. As loss of lipid asymmetry is important in cell survival and protein reconstitution, these results highlight the importance of methanol in proteolipidic studies.
Biophysical Journal


Lipid membranes, asymmetry, flip-flop, kinetics, small angle neutron scattering


Nguyen, M. , DiPasquale, M. , Rickeard, B. , Stanley, C. , Kelley, E. and Marquardt, D. (2019), Methanol Accelerates DMPC Flip-Flop and Transfer: A SANS Study on Lipid Dynamics, Biophysical Journal, [online], (Accessed June 22, 2024)


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Created March 4, 2019, Updated October 12, 2021