Interplay between elastic and structural properties in cholesterol-rich lipid membranes

Cholesterol is a vital component of cell membranes and a common additive in artificial lipid membranes. Structurally, cholesterol is known to increase lipid ordering and decrease the area per lipid, A_L, in fluid lipid membranes. Despite these unified structural effects, cholesterol’s influence on the membrane bending modulus, κ,<!--[if gte msEquation 12]> style='mso-bidi-font-style:normal'>_κ, has been reported to vary with lipid chain unsaturation – presenting a dilemma for structure-property relations. To address this, we examined the interdependence of cholesterol-driven changes in structural and elastic membrane properties on mesoscopic scales using neutron spin-echo spectroscopy, combined with MD simulations and solid-state ²H NMR spectroscopy. Our results clearly show that cholesterol stiffens all studied membranes, irrespective of chain unsaturation. More importantly, by mapping these observations to those from small-angle X-ray scattering studies, we find that the measured changes in κ<!--[if gte msEquation 12]> style='mso-bidi-font-style:normal'>_κ, normalized against cholesterol-free membranes, correlate with changes in A_L via a universal scaling law. Such scaling relations are transformative on biological and technological fronts, enabling predictions of elastic properties of complex biological membranes and accelerating the design rules of engineered membranes with tunable functionalities.