Speaker
Richard Alsop
(McMaster University)
Description
All drugs must cross the lipid membrane to enter the cell, either by passive or active transport. Diffusing drug molecules may interact with, or embed in, the bilayer and change membrane structure and function. We have observed a significant interaction between cholesterol and the common analgesic, ibuprofen, in model lipid membranes [1]. Using X-ray diffraction in highly oriented, multi-lamellar stacks of lipid membranes, we located the ibuprofen molecule within the bilayer and determined that the drug induces a lamellar to cubic phase transition at concentrations of more than 5 mol%. The phase transition is caused by the presence of ibuprofen in the hydrophobic membrane core, where it induces negative membrane curvature.
Cholesterol is a stiff, hydrophobic sterol molecule which also embeds within the membrane core and stiffens lipid tails [2]. When ibuprofen is introduced into membranes prepared with 20 mol% cholesterol, the cubic phase transition is suppressed, as ibuprofen is not able to partition into the core of cholesterol-containing membranes. The results indicate that ibuprofen-membrane interactions strongly depend on membrane composition and properties. The work adds to the growing evidence that amphiphilic molecules, such as aspirin or ibuprofen, significantly disrupt membrane structure [3,4].
[1] **RJ Alsop** *et al*. Soft Matter (2015). 11(24) 4756-4767.
[2] MA Barrett, S Zheng, LA Toppozini, **RJ Alsop**, *et al*. Soft Matter (2013). 9(39) 9342-9351.
[3] **RJ Alsop** *et al*. Soft Matter (2014). 10(24) 4275-4286.
[4] **RJ Alsop** *et al*. BBA-Biomembranes (2015). 1848. 805-812.
Authors
Maikel Rheinstadter
(McMaster University)
Richard Alsop
(McMaster University)
