BPS2026 – Characterizing interactions between glycoproteins and RNA at the lipid membrane interface

Biological membranes are highly dynamic environments composed of a diverse array of lipids that vary in chemistry and actively participate in cellular functions. The interactions of proteins, nucleic acids, and glycans at the lipid membrane interface are integral to many cellular processes. The interplay between membrane lipids and biomolecules is highly sensitive to their flexibility grade, secondary structure, and biophysical and electrostatic properties. Consequently, the cell membrane interface experiences changes in local lipid distribution and fluctuation in local properties. Projecting biophysical and structural membrane and biopolymer properties onto a two-dimensional plane simplifies the quantification of molecular signatures by reducing the dimensional space and identifying relevant entropic and short-range interactions at the interface of interest. Molecular dynamics simulations generate large data sets of the temporal evolution of molecular systems. Here, we leverage the capabilities of 2D analysis, a toolbox designed to project membrane and biopolymer properties onto a two-dimensional plane, to characterize interaction patterns and spatial correlations of complex lipid bilayers as they interact with biomolecules. We compare lipid-lipid interaction patterns in membrane-only systems to the corresponding systems containing small proteins and RNA fragments, respectively. These analyses quantify the effect of peripheral biomolecules on local lipid composition, structure, packing, and surface topology of the membrane upon adsorption. Such characterization is crucial for the rational design of lipid vesicles and lipid-coated drug delivery systems for nucleic acids. Given the transfection efficiency of such systems may be linked to membrane stability, molecular insights into lipid-biomolecule interactions could inform strategies to stabilize the membrane and enhance drug delivery performance.