Thermo-responsiveness of auto-oxidized cholesterol-containing lipid membranes, observed in real-time

There are increasing many reports linking oxidation of the membrane to various diseases such as atherosclerosis. Using cell-sized (giant) unilamellar lipid vesicles, we studied the effect of exposing the lipid vesicles to an oxidative stress environment. We found that the vesicles underwent fluctuations, and some had morphological transformation. We characterized the main products of cholesterol oxidation as 7β-hydroxycholesterol (7β) and 7-ketocholesterol (7keto). After, we prepared lipid membrane containing the above oxy-cholesterols and investigated the influence of temperature on membrane dynamics. We found that (i) 7b and 7keto rendered vesicles more responsive to temperature changes, (ii) 7keto imparted greater thermo-induced membrane dynamics than 7β, (iii) 7b and 7keto vesicles synergistically, were more thermo-responsive than the individual oxysterols, (iv) the thermo-responsiveness of 7keto-containing vesicles was equivalent to that of 25 hydroxycholesterol (25OH)-containing vesicles, In addition, we carried out langmuir monolayer experiments using the membrane systems above. The results show an increase in molecular area with increase in temperature. and correlated well with the membrane dynamics upon temperature change. These results are important to understanding mechanisms of membrane dynamics upon oxidative stress. The interplay between cholesterol oxidation and temperature provides new ideas for development of oxidative stimulus-dependent therapeutics, including thermo therapy.