Surface ripples cause the large fluid spaces between gel phase bilayers containing small amounts of cholesterol

Previous studies have found that small concentrations of cholesterol, or several other molecules such as benzene and asialoganglioside, dramatically increase the fluid separation between gel phase phosphatidylcholine bilayers. These observations can not be explained in terms of changes in the repulsive and attractive pressures known to exist between flat gel phase bilayer surfaces. We show here that the increase in fluid space occurs as a consequence of cholesterol inducing large periodic ripples in the plane of the bilayer. The analysis of Mortensen et al. (Biochim. Biophys. Acta 945, 221-245) indicates that the sides of the ripples primarily contain gel phase phosphatidylcholine, whereas the apices are enriched in cholesterol and are liquid-crystalline. We argue that the large fluid spaces can be explained by steric repulsion between adjacent bilayers caused both by thermally induced accordion-like motions of these ripples and defects in the ripple organization. In addition, ripples potentially can decrease van der Waals attraction and change hydration repulsion between bilayers.