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Investigating the Cut-off Effect of n-alcohols on Lipid Movement: A Biophysical Study



Michael H. Nguyen, Dominik Dziura, Mitchell DiPasquale, Stuart R. Castillo, Elizabeth Kelley, Drew Marquardt


Cellular membranes are responsible for absorbing the effects of external perturbants for the cell's survival. Such perturbants include small ubiquitous molecules like n-alcohols which were observed to exhibit anesthetic capabilities, with this effect tailoring off at a cut-off alcohol chain length. To explain this cut-off effect and compliment prior biochemical studies, we investigated their impact on several bilayer properties, including lipid flip-flop, intervesicular exchange, diffusion, membrane bending rigidity and more. To this end, we employed an array of biophysical techniques such as time-resolved small angle neutron scattering (TR-SANS), small angle X-ray scattering (SAXS), all-atomistic and coarse-grained molecular dynamics (MD) simulations, and calcein leakage assays. First, TR-SANS showed transverse lipid diffusion, i.e. flip-flop, exhibited an increase in flip-flop rates as alcohol chain length increased but steeply slowed with carbon lengths of C10 and above. Intervesicular lipid exchange contrasted these results with only a slight cut-off at alcohol concentrations of 9 mmol/L but not 2 mmol/L. SAXS, MD simulations, and leakage assays revealed changes to key bilayer properties, such as bilayer thickness and fluidity, that correlate well with the effects on lipid flip-flop rates. Finally, we tie our results to a defect-mediated pathway for alcohol-induced lipid flip-flop.
Soft Matter


n-alcohols, lipid membrane, TR-SANS, lipid exchange, lipid flip-flop, kinetics, MD simulations


Nguyen, M. , Dziura, D. , DiPasquale, M. , Castillo, S. , Kelley, E. and Marquardt, D. (2023), Investigating the Cut-off Effect of n-alcohols on Lipid Movement: A Biophysical Study, Soft Matter, [online], (Accessed July 15, 2024)


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Created July 5, 2023, Updated January 23, 2024