Understanding How Sterols Regulate Membrane Remodeling in Supported Lipid Bilayers

The addition of single-chain lipid amphiphiles such as antimicrobial fatty acids and monoglycerides to confined, two-dimensional phospholipid bilayers can trigger the formation of three-dimensional membrane morphologies as a passive means to regulate stress. To date, relevant experimental studies have been conducted using pure phospholipid compositions, and extending such insights to more complex, biologically relevant lipid compositions that include phospholipids and sterols is warranted because sterols are important biological mediators of membrane stress relaxation. Herein, using the quartz crystal microbalancedissipation (QCM-D) technique, we investigated membrane remodeling behaviors triggered by the addition of sodium dodecyl sulfate (SDS), lauric acid (LA), and glycerol monolaurate (GML) to supported lipid bilayers (SLBs) composed of phospholipid and cholesterol mixtures. The SLB platforms were prepared by the solvent-assisted lipid bilayer method in order to form cholesterol-rich SLBs with tunable cholesterol fractions (0-52 mol %). The addition of SDS or LA to fabricated SLBs induced tubule formation, and the extent of membrane remodeling was greater in SLBs with higher cholesterol fractions. In marked contrast, GML addition led to bud formation, and the extent of membrane remodeling was lower in SLBs with higher cholesterol fractions. To explain these empirical observations, we discuss how cholesterol influences the elastic (stiffness) and viscous (stress relaxation) properties of phospholipid/cholesterol lipid bilayers as well as how the membrane translocation properties of single-chain lipid amphiphiles affect the corresponding membrane morphological responses. Collectively, our findings demonstrate that single-chain lipid amphiphiles induce highly specific membrane morphological responses across both simplified and complex model membranes, and cholesterol can promote or inhibit membrane remodeling by a variety of molecular mechanisms.