Syndecans are heparan sulfate proteoglycans (HSPGs) that regulate many cellular processes through their localization in lipid rafts and interactions with over 360 binding partners. However, the structural mechanisms by which Syndecans influence glycocalyx dynamics remain poorly understood. Gangliosides, such as GM1, are enriched in neuronal membranes where they influence lipid raft stability and protein partitioning. Syndecans localize to these domains, and both have been implicated in amyloid-β aggregation and uptake. In this work, we perform large-scale molecular dynamics (MD) simulations of model neuronal membranes containing gangliosides (GM1 and β-galactosyl-ceramide) and Syndecans, where a membrane system without Syndecans serves as a control. We assess how Syndecans alter membrane properties by quantifying lipid lateral diffusion, bilayer thickness, protein-lipid interactions and glycan conformational dynamics. Establishing this baseline characterization of Syndecan-mediated membrane dynamics provides a computational framework to quantify how Syndecans remodel the glycocalyx environment. Because both gangliosides and Syndecans are known modulators of protein aggregation at the cell surface, this framework lays groundwork for future studies of amyloid-membrane interactions and potential synergistic effects between gangliosides, glycans and amyloid-β peptides.

Anne Brown

Virginia Polytechnic Institute and State University

Appearances