Thermotropic behavior of galactosylceramides with cis-monoenoic fatty acyl chains - PubMed (original) (raw)
Thermotropic behavior of galactosylceramides with cis-monoenoic fatty acyl chains
V S Kulkarni et al. Biochim Biophys Acta. 1998.
Abstract
To define the thermotropic behavior of galactosylceramides (GalCer) containing cis monounsaturated acyl chains, N-X:1Delta(X-9) cis galactosylsphingosines (GalSph) were synthesized (where X=24, 22, 20, or 18) and investigated by differential scanning calorimetry (DSC). After hydration of dried glycolipid, aqueous dispersions were prepared by repetitive heating and freeze-thaw cycles. The DSC data clearly showed that introducing a single cis double bond into the acyl chain of GalCer lowers the transition temperature of the main endothermic peak and affects the kinetics of formation of various metastable and stable gel phases. More importantly, the data emphasize the role that double bond location in concert with acyl chain length play in modulating the thermotropic behavior of GalCers. In contrast to the 18:1 GalCer and 20:1 GalCer endotherms which remain unchanged after identical repetitive heating scans and low temperature incubations, the thermotropic responses of 22:1 GalCer and 24:1 GalCer depended directly upon incubation time at lower temperatures following a heating scan. Only after extended incubation (4-5 days) did the endotherms revert to behavior observed during the initial heating scan that followed sample preparation by cyclic heating and freeze-thaw methods. The extended incubation times required for 22:1 GalCer and 24:1 GalCer to assume their more stable packing motifs appear to be consistent with nucleation events that promote transbilayer interdigitation. Yet, due to the slow kinetics of the process, the presence of cis monounsaturation in very long acyl chains that are common to GalCer may effectively inhibit transbilayer lipid interdigitation under physiological conditions.
Figures
Fig. 1
DSC thermotropic behavior of 24:1 GalCer. All traces represent heating scans run at a rate of 10°C/h. Glycolipid aqueous dispersions were produced by the freeze-thaw and heat cycling protocol described in Section 2. (A) Freshly prepared 24:1 GalCer dispersion incubated for 3 h at 4°C prior to initiating the heating scan; (B) 24:1 GalCer dispersion incubated for 3 days at 22°C following an initial heating scan as described in A; (C) 24:1 GalCer dispersion incubated for 100 min at 4°C following an initial heating scan as described in A; (D) 24:1 GalCer dispersion incubated for 5 days at 22°C following an initial heating scan as described in A.
Fig. 2
DSC thermotropic behavior of 22:1 GalCer. All traces represent heating scans run at a rate of 10°C/h. Glycolipid aqueous dispersions were produced by the freeze-thaw and heat cycling protocol described in Section 2. (A) Freshly prepared 22:1 GalCer dispersion incubated for 3 h at 4°C prior to initiating the heating scan; (B) 22:1 GalCer dispersion incubated for 100 min at 4°C following an initial heating scan as described in A; (C) 22:1 GalCer dispersion incubated for 3 days at 22°C following an initial heating scan as described in A.
Fig. 3
DSC thermotropic behavior of 20:1 GalCer. All traces represent heating scans run at a rate of 10°C/h. Glycolipid aqueous dispersions were produced by the freeze-thaw and heat cycling protocol described in Section 2. (A) Freshly prepared 20:1 GalCer dispersion incubated for 3 h at 4°C prior to initiating the heating scan; (B) 20:1 GalCer dispersion incubated for 100 min at 4°C following an initial heating scan as described in A; (C) 20:1 GalCer dispersion incubated for 4 days at 22°C following an initial heating scan as described in A.
Fig. 4
DSC thermotropic behavior of 18:1 GalCer. All traces represent heating scans run at a rate of 10°C/h. Glycolipid aqueous dispersions were produced by the freeze-thaw and heat cycling protocol described in Section 2. (A) Freshly prepared 18:1 GalCer dispersion incubated for 3 h at 4°C prior to initiating the heating scan; (B) 18:1 GalCer dispersion incubated for 100 min at 4°C following an initial heating scan as described in A; (C) 18:1 GalCer dispersion incubated for 4 days at 22°C following an initial heating scan as described in A.
Fig. 5
Schematic representation of GalCer derivatives with monounsaturated acyl chains illustrating the possibilities for transbilayer hydrocarbon interdigitation. Hydrocarbon conformations are based on the NMR, diffraction, and MM3 modeling studies referred to in the text. For simplicity, long axis molecular tilt and headgroup conformation are not depicted although diffraction data and MM3 modeling data indicate that a bent ‘shovel’ conformation is likely in the stable gel phase in which the headgroup lies roughly parallel to the interfacial plane for GalCer lamellar crystalline phase(s) [48,67,68]. The transition from the liquid-crystalline phase to the stable gel phase leads to reorientation of the galactose [68]. In the schematic, the small black filled circle represents nitrogen and the small unfilled circle represents oxygen. Based on these conformational models, partial interdigitation of the hydrocarbon chains would be predicted for 24:1 GalCer and 22:1 GalCer, but not 20:1 GalCer or 18:1 GalCer.
References
- Harouse JM, Bhat S, Spitalnik SL, Laughlin M, Sefano K, Silberberg DH, Gonzalez-Scarano F. Inhibition of entry of HIV-1 in neural cell lines by antibodies against galactosyl ceramide. Science. 1991;253:320–323. - PubMed
- Cook DG, Fantini J, Spitalnik SL, Gonzalez-Scarano F. Binding of human immunodeficiency virus type 1 (HIV-1) gp120 to galactosylceramide (GalCer): relationship to the V3 loop. Virology. 1994;201:206–214. - PubMed
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources