We studied the interaction of Aspirin (acetylsalicylic acid) with lipid membranes using x-ray diffraction for bilayers containing up to 50 mol% of aspirin. From 2D x-ray intensity maps that cover large areas of reciprocal space we determined the position of the ASA molecules in the phospholipid bilayers and the molecular arrangement of the molecules in the plane of the membranes. We present direct experimental evidence that ASA molecules participate in saturated lipid bilayers of DMPC (1,2-dimyristoyl-sn-glycero-3-phosphocholine) and preferably reside in the head group region of the membrane. Up to 50 mol% ASA molecules can be dissolved in this type of bilayer before the lateral membrane organization is disturbed and the membranes are found to form an ordered, 2D crystal-like structure. Furthermore, ASA and cholesterol were found to co-exist in saturated lipid bilayers, with the ASA molecules residing in the head group region and the cholesterol molecules participating in the hydrophobic membrane core.

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We present a combined neutron and X-ray scattering investigation to study the effect of ethanol on the molecular structure and dynamics of lipid membranes. 1,2-Dimyristoyl-sn-glycero-3phoshatidylcholine (DMPC) powder hydrated with a 5 wt% ethanol solution (corresponding to 2 mol% of ethanol) was used in this study. From high-resolution X-ray experiments the position and partitioning of the ethanol molecules in the phospholipid bilayers was determined in their gel and fluid phases. We find that the ethanol molecules reside in the head group region of the bilayers, with 1.6 ethanol molecules per lipid molecule in the gel phase and 1.2 ethanol molecules per lipid molecule in the fluid phase. We find evidence for enhanced permeability in both fluid and gel phases of the phospholipid bilayers in the presence of ethanol molecules. Elastic and quasi-elastic neutron scattering data, obtained using a neutron backscattering spectrometer, was used to study slow, nanosecond molecular dynamics on length scales corresponding to lipid diffusion, acyl chain dynamics and solvent dynamics. While the presence of ethanol molecules had no observable effect on these types of dynamics in the fluid (L a ) phase, the membranes appeared to have a higher degree of order in gel (L b ) and ripple (P b 0 ) phases. In particular, lipid diffusion was found to be slower by a factor of two in the more rigid gel phase when ethanol was present.

Cholesterol has been well established as a mediator of cell membrane fluidity. By interacting with lipid tails, cholesterol causes the membrane tails to be constrained thereby reducing membrane fluidity, well known as the condensation effect. Acetylsalicylic acid (ASA), the main ingredient in aspirin, has recently been shown to increase fluidity in lipid bilayers by primarily interacting with lipid head groups. We used high-resolution X-ray diffraction to study both ASA and cholesterol coexisting in model membranes of dimyristoylphosphatidylcholine (DMPC). While a high cholesterol concentration of 40 mol% cholesterol leads to the formation of immiscible cholesterol bilayers, as was reported previously, increasing the amount of ASA in the membranes between 0 to 12.5 mol% was found to significantly increase the fluidity of the bilayers and dissolve the cholesterol plaques. We, therefore, present experimental evidence for an interaction between cholesterol and ASA on the level of the cell membrane at elevated levels of cholesterol and ASA.