The impact of the glycan headgroup on the nanoscopic segregation of gangliosides

0549941 - ÚFCH JH 2022 RIV US eng J - Článek v odborném periodiku
Sarmento, Maria Joäo - Owen, M. C. - Ricardo, Joana Catarina - Chmelová, Barbora - Davidović, David - Mikhalyov, I. - Gretskaya, N. - Hof, Martin - Amaro, Mariana - Vácha, R. - Šachl, Radek
The impact of the glycan headgroup on the nanoscopic segregation of gangliosides.
Biophysical Journal. Roč. 120, č. 24 (2021), s. 5530-5543. ISSN 0006-3495. E-ISSN 1542-0086
Grant CEP: GA ČR(CZ) GX19-26854X; GA ČR(CZ) GC20-01401J
Grant ostatní: Ga MŠk(CZ) LM2015070; GA MŠk(CZ) LM2015042; GA MŠk(CZ) LM2015085; Ministerstvo školství, mládeže a tělovýchovy - GA MŠk(CZ) LM2018140
Institucionální podpora: RVO:61388955
Klíčová slova: gangliosides * lipid membranes * oligosacharide
Obor OECD: Physical chemistry
Impakt faktor: 3.699, rok: 2021
Způsob publikování: Omezený přístup

Gangliosides form an important class of receptor lipids containing a large oligosaccharide headgroup whose ability to self-organize within lipid membranes results in the formation of nanoscopic platforms. Despite their biological importance, the molecular basis for the nanoscopic segregation of gangliosides is not clear. In this work, we investigated the role of the ganglioside headgroup on the nanoscale organization of gangliosides. We studied the effect of the reduction in the number of sugar units of the ganglioside oligosaccharide chain on the ability of gangliosides GM1, GM2, and GM3 to spontaneously self-organize into lipid nanodomains. To reach nanoscopic resolution and to identify molecular forces that drive ganglioside segregation, we combined an experimental technique, Förster resonance energy transfer analyzed by Monte-Carlo simulations offering high lateral and trans-bilayer resolution with molecular dynamics simulations. We show that the ganglioside headgroup plays a key role in ganglioside self-assembly despite the negative charge of the sialic acid group. The nanodomains range from 7 to 120 nm in radius and are mostly composed of the surrounding bulk lipids, with gangliosides being a minor component of the nanodomains. The interactions between gangliosides are dominated by the hydrogen bonding network between the headgroups, which facilitates ganglioside clustering. The N-acetylgalactosamine sugar moiety of GM2, however, seems to impair the stability of these clusters by disrupting hydrogen bonding of neighboring sugars, which is in agreement with a broad size distribution of GM2 nanodomains. The simulations suggest that the formation of nanodomains is likely accompanied by several conformational changes in the gangliosides, which, however, have little impact on the solvent exposure of these receptor groups. Overall, this work identifies the key physicochemical factors that drive nanoscopic segregation of gangliosides.
Trvalý link: http://hdl.handle.net/11104/0325833