BPS2026 – Model membranes derived from human red blood cells for use as targets in viral binding and fusion studies

Red blood cells (RBCs) circulate through nearly every tissue of the human body and interactions between the RBC membrane and foreign pathogens are central to many human diseases. Direct study of RBC-pathogen interactions using surface-sensitive biophysical and biochemical techniques would greatly enable improved understanding of these interactions in their native environment. Here, we present approaches for preparing two types of surface-attached model lipid membranes derived from RBC-supported lipid bilayers (RBC-SLBs) and tethered RBC liposomes—with the goal to use them as target membranes in the study of viral binding and membrane fusion. Importantly, these model membranes preserve key components of the native RBC membrane. We validate and characterize the functionality of these membranes by quantification of lipid mobility, analysis of the distribution and dynamics of the glycophorin A membrane protein, and assessment of the activity of the acetylcholinesterase enzyme. We present preliminary data using RBC-SLBs as binding targets for a viral pathogen (Sendai virus) and progress toward using the tethered RBC liposomes as targets to study viral fusion. We anticipate that our results and methodologies will be of particular interest to researchers studying viral binding and membrane fusion, more broadly to researchers engineering model membrane platforms derived from physiological membranes, as well as those interested in the study of molecular interactions with RBC membranes.