The effect of oxycholesterols on thermo-induced membrane dynamics

Abstract

The effect of temperature change(s) on the dynamics of giant unilamellar vesicles containing oxidized and non-oxidized cholesterol was investigated and characterized. We have demonstrated that (i) major cholesterol auto-oxidation products, 7β-hydroxycholesterol (7β) and 7-ketocholesterol (7keto), rendered vesicles more responsive to temperature changes; (ii) 7keto imparted greater thermo-induced membrane dynamics than 7β; (iii) 7β 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; and (v) we have characterized the observed membrane dynamics. The results provide a new plausible mechanism: oxidative-stressed membranes in conjunction with temperature change induce membrane dynamics. These findings improve the mechanisms reported previously that attributed the induced dynamics solely to membrane oxidation.

Thermo‐induced Vesicular Dynamics of Membranes Containing Cholesterol Derivatives

“…In fact, it has been reported that oxidized cholesterol (OxyCHOL) renders membranes unstable more than non-oxidized cholesterol-containing systems [3,4]. In a recent study, we investigated the thermo-responsiveness of OxyCHOL in lipid vesicles [5]. We observed changes in membrane perturbation and we proposed a mechanism behind the change in stability.…”

“…We had reported that 7KC was one of major derivatives of cholesterol after oxidative stress [5]. It has been reported that this OxyCHOL is related to crystal formation on macrophages and even muscles [27].…”

“…Membrane structural re-organization and re-packing can be induced by various forms of stimuli such as oxidation, light, and temperature [5,[8][9][10][11][12]. Rafts are considered to be a form of order-disorder phase separation that develop due to the interaction between lipid molecules.…”

“…7-Ketocholesterol (7KC) and 7bHC are produced by reactive oxygen species. 25-Hydroxycholesterol (25HC) is oxidized enzymatically [5,16]. BENZO is an artificial cholesterol derivative [18] Scheme 2 Similarity of structure between cholesterol liquid crystal CHOL PA and CHOL OC and phospholipid DOPC.…”

“…However, there is lot yet to be understood about membrane dynamic processes. Cell-sized lipid vesicles have been use to study the effect of different types of stresses on membrane stability [5,8,9,[21][22][23][24]. The cellsized vesicles allow real-time observation of dynamic morphological changes to be clearly visualized, without compromising the ''controllable'' analytical advantage [2].…”