Membrane-wrapped nanoparticles probe divergent roles of GM3 and phosphatidylserine in lipid-mediated viral entry pathways

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 115; no. 39; pp. E9041 - E9050
• Main Authors: Xu, Fangda, Bandara, Asanga, Akiyama, Hisashi, Eshaghi, Behnaz, Stelter, David, Keyes, Tom, Straub, John E., Gummuluru, Suryaram, Reinhard, Björn M.
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 25-09-2018
• Series: PNAS Plus
• Subjects: Binding; Biological properties; Biological Sciences; Bleaching; CD9 antigen; Compartments; G(M3) Ganglioside - metabolism; Gold; HIV; Human immunodeficiency virus; Humans; Lipids; Liposomes; Localization; Lysosomes - metabolism; Lysosomes - virology; Macrophages; Macrophages - metabolism; Macrophages - virology; Membrane composition; Membranes; Membranes, Artificial; Metal Nanoparticles; Molecular dynamics; Nanomaterials; Nanoparticles; Nanotechnology; Optical properties; Phosphatidylserine; Phosphatidylserines - metabolism; Physical properties; Physical Sciences; PNAS Plus; Self-assembly; Sialic Acid Binding Ig-like Lectin 1 - metabolism; Surface properties; Tetraspanin 29 - metabolism; THP-1 Cells; Virus Internalization; Viruses; Viruses - metabolism; HIV-1; glycolipids; apoptotic mimicry; bioplasmonics; virus-containing compartments
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.1804292115

Gold nanoparticles (NPs) wrapped in a membrane can be utilized as artificial virus nanoparticles (AVNs) that combine the large nonblinking or bleaching optical cross-section of the NP core with the biological surface properties and functionalities provided by a self-assembled lipid membrane. We used these hybrid nanomaterials to test the roles of monosialodihexosylganglioside (GM3) and phosphatidylserine (PS) for a lipid-mediated targeting of virus-containing compartments (VCCs) in macrophages. GM3-presenting AVNs bind to CD169 (Siglec-1)–expressing macrophages, but inclusion of PS in the GM3-containing AVN membrane decreases binding. Molecular dynamics simulations of the AVN membrane and experimental binding studies of CD169 to GM3-presenting AVNs reveal Na⁺-mediated interactions between GM3 and PS as a potential cause of the antagonistic action on binding by the two negatively charged lipids. GM3-functionalized AVNs with no or low PS content localize to tetherin⁺, CD9⁺ VCC in a membrane composition-depending fashion, but increasing amounts of PS in the AVN membrane redirect the NP to lysosomal compartments. Interestingly, this compartmentalization is highly GM3 specific. Even AVNs presenting the related monosialotetrahexosylganglioside (GM1) fail to achieve an accumulation in VCC. AVN localization to VCC was observed for AVN with gold NP core but not for liposomes, suggesting that NP sequestration into VCC has additional requirements beyond ligand (GM3)–receptor (CD169) recognition that are related to the physical properties of the NP core. Our results confirm AVN as a scalable platform for elucidating the mechanisms of lipid-mediated viral entry pathways and for selective intracellular targeting.