Aspirin Interacts with Cholesterol-Containing Membranes in a pH-Dependent Manner

Abstract

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-2oleoyl-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.

Concentration-Dependent Effects of Curcumin on Membrane Permeability and Structure

“…By using water as a molecular probe, the DIB offers a flexible platform to explore the influence of the lipid structure on passive permeation through bilayer aggregates. Our observations indicate that water transport across a single unsupported bilayer is highly responsive to the physical state of model membranes, revealing subtle compositional and structural effects, − and selective influence of exogenous bioactive molecules. − …”

Differential Effects of Soy Isoflavones on the Biophysical Properties of Model Membranes

“…Through the use of water as a molecular probe, we illustrated that the rate at which water traverses a bilayer is highly responsive to the physical state of cell membranes. Consequently, delving into water permeability studies can significantly enrich our comprehension of the intrinsic barrier properties inherent in membrane architecture. − In recent studies, we have also investigated the effects of a wide range of biologically important molecules on membrane permeability and, in turn, membrane structure. − Our previous studies have shown the intriguing ability of bioactive molecules and phytochemicals to sensitively and variously respond to model membranes of diverse compositions in modulating physical properties such as transbilayer water permeability and thermodynamic, structural, and surface properties.…”

“… 43 − 46 In recent studies, we have also investigated the effects of a wide range of biologically important molecules on membrane permeability and, in turn, membrane structure. 47 − 50 Our previous studies have shown the intriguing ability of bioactive molecules and phytochemicals to sensitively and variously respond to model membranes of diverse compositions in modulating physical properties such as transbilayer water permeability and thermodynamic, structural, and surface properties.…”