Paper BI-ThM6
Effects of Fluidity on HIV-1 Neutralizing Antibody Binding to Membrane Surfaces

Thursday, October 18, 2007, 9:40 am, Room 609

Recent studies show that HIV-1 may take advantage of the phenomenon that healthy individuals do not normally produce self reactive antibodies. Broadly neutralizing monoclonal antibodies (nAbs) 4E10 and 2F5 bind to epitopes in the membrane proximal external region (MPER) on the HIV-1 transmembrane envelope glycoprotein (Env) gp41. Unlike most antibodies, however, they also react with several common membrane phospholipids. This auto-reactive characteristic may explain why they are rarely (if ever) found in HIV-1 patients. Little is known about the mechanics of these interactions between nAb and membrane. Initial surface plasmon resonance (SPR) studies suggest a two phase binding model where the nAb first encounters the membrane epitope proximal region, and then docks more securely in a second step. One theory for the mechanism behind this model suggests nAb may first bind to lipid, then diffuse on the lipid until encountering the MPER region on Env gp41. In our work, we investigate the effects of membrane fluidity in this process. Increasing temperature adversely affects this interaction, as it increases the on-rate, but more rapidly increases the off-rates. In order to eliminate rate effects, we monitor protein binding to peptide sequences embedded in mobile supported lipid bilayers and in static lipid monolayer surfaces. Quartz crystal microbalance with dissipation monitoring (QCM-D) was used to verify bilayer and monolayer formation as well as to measure nAb binding. This knowledge will provide insight into the mechanism of nAb-lipid binding, which may facilitate the production of effective HIV-1 therapies.