Cell-surface anionic membranes and heparan sulfate proteoglycans (HSPG)

Cell-surface anionic membranes and heparan sulfate proteoglycans (HSPGs) constitute a negatively charged interface on the plasma membrane that plays a pivotal role in cellular communication and pathogen entry. HSPGs, including the syndecan and glypican families, consist of core proteins decorated with heparan sulfate glycosaminoglycan chains that bind a diverse array of ligands such as growth factors, cytokines, and extracellular matrix components (Sarrazin et al., 2011, Cold Spring Harb Perspect Biol). The anionic charge of these membranes, contributed by both the sulfate groups on HSPGs and acidic phospholipids, facilitates the initial electrostatic recruitment of cationic molecules, including cell-penetrating peptides and viral attachment proteins (Magzoub & Gräslund, 2004, Q Rev Biophys). Many viruses, such as SARS-CoV-2, HIV-1, and Herpes Simplex Virus, utilize HSPGs as primary attachment receptors to concentrate viral particles on the cell surface before engaging specific entry receptors (Cagno et al., 2019, Rev Med Virol). In therapeutic contexts, these structures are targeted by polyanionic mimetics or cationic peptides to block viral infection, inhibit tumor angiogenesis, or facilitate the delivery of macromolecular drugs (Wadajkar et al., 2013, J Control Release).

Other names

Cell-surface glycansHeparan sulfateSyndecansGlypicansAnionic phospholipidsCell-surface glycosaminoglycans

Competitive inhibition of ligand binding to heparan sulfate chains and electrostatic neutralization of anionic membrane surfaces to prevent viral or molecular entry.