posted on 2023-11-08, 22:05authored byMichael Krmic, Escarlin Perez, Patrick Scollan, Katherine Ivanchenko, Alondra Gamez Hernandez, Joseph Giancaspro, Juan Rosario, Jasmin Ceja-Vega, Jamie Gudyka, Riley Porteus, Sunghee Lee
Aspirin has been
used for broad therapeutic treatment, including
secondary prevention of cardiovascular disease associated with increased
cholesterol levels. Aspirin and other nonsteroidal anti-inflammatory
drugs have been shown to interact with lipid membranes and change
their biophysical properties. In this study, mixed lipid model bilayers
made from 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylcholine
(POPC) or 1,2-dioleoyl-sn-glycero-3-phosphatidylcholine
(DOPC) comprising varying concentrations of cholesterol (10:1, 4:1,
and 1:1 mole ratio of lipid:chol), prepared by the droplet interface
bilayer method, were used to examine the effects of aspirin at various
pH on transbilayer water permeability. The presence of aspirin increases
the water permeability of POPC bilayers in a concentration-dependent
manner, with a greater magnitude of increase at pH 3 compared to pH
7. In the presence of cholesterol, aspirin is similarly shown to increase
water permeability; however, the extent of the increase depends on
both the concentration of cholesterol and the pH, with the least pronounced
enhancement in water permeability at high cholesterol levels at pH
7. A fusion of data from differential scanning calorimetry, confocal
Raman microspectrophotometry, and interfacial tensiometric measurements
demonstrates that aspirin can promote significant thermal, structural,
and interfacial property perturbations in the mixed-lipid POPC or
DOPC membranes containing cholesterol, indicating a disordering effect
on the lipid membranes. Our findings suggest that aspirin fluidizes
phosphocholine membranes in both cholesterol-free and cholesterol-enriched
states and that the overall effect is greater when aspirin is in a
neutral state. These results confer a deeper comprehension of the
divergent effects of aspirin on biological membranes having heterogeneous
compositions, under varying physiological pH and different cholesterol
compositions, with implications for a better understanding of the
gastrointestinal toxicity induced by the long term use of this important
nonsteroidal anti-inflammatory molecule.