Probing Insertion and Solubilization Effects of Lysolipids on Supported Lipid Bilayers Using Microcantilevers

Abstract

The interaction of surfactants with lipid membranes can result in composition change, area expansion, solubilization, or the formation of protrusion features of the membranes. Amphipathic surfactant molecules are simplified analogues to membrane-active drugs and peptides which are known for inserting into lipid bilayers; however, the effect of these amphipathic molecules on supported membranes is not well characterized. In this paper we explore the use of microcantilever sensors to quantify surfactants' effects on lipid membranes. We use microcantilevers which are coated with lipid membranes to probe the interactions between lysolipids and supported lipid bilayers (SLBs). In particular, we investigate the effects of four zwitterionic surfactants similar to phospholipids: lysolipids of different aliphatic chain lengths (lysophosphocholines, lysoPCs, 12:0, 14:0, 16:0, and 18:0) on 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine-supported lipid bilayers. By monitoring the deflection of the microcantilevers, real-time free energy changes in the SLBs upon the addition of lysolipids can be detected. Additionally, the bending direction reveals whether the lysoPCs incorporate into or solubilize the SLB. When the bulk lysoPC concentration is less than its critical micelle concentration (CMC), we observe a compressive bending of the microcantilever, indicating adsorption to the SLB. Additionally, the change in surface stress is found to be proportional to the amount of membrane-bound lysoPCs. For bulk concentrations greater than the CMC, lysoPCs 12:0 and 14:0, there is tensile bending, indicating that the lysoPCs begin to solubilize and destroy the SLBs. Interestingly, this is not observed for lysoPCs with longer chain lengths. This new method of using microcantilevers for detecting and quantifying the surfactant insertion and solubilization of SLBs offers additional insights into the interactions between small amphipathic molecules and lipid membranes.