Structure of Supramers Formed by Glycolipid Analogues: SAXS Study

Synthetic glycolipids and similar amphiphils with peptide and other head groups have been designed for labeling/modification of living cells under mild physiological conditions. Under-standing the mechanism of their penetration through the cellular glycocalyx and subsequent insertion into the plasma membrane opens up the prospect of improving the recently found anti-tumor properties of such constructs. In this work, we applied small-angle X-ray scattering (SAXS) technique to characterize structure of nanoparticles formed by self-assembly of synthetic glycolipid A (type 2)-Ad-DE and to estimate its dependence on the glycolipid concentration. The studies were performed at a range of SAXS-applicable concentrations. The obtained results indicate that self-assembly process leads to formation of monodisperse nanoparticles with micelle-like architecture, which is maintained regardless of concentration, indicating absence of the nanoparticle’s positive interaction with their glycopart. We applied ab initio modeling that showed a good agreement with experimental data, and found that the ellipsoid monodisperse nanoparticles have a size of about 14 nm. Quasi-atomic modeling visualised that glycan ligands are well accessed for biological recognition. This knowledge will facilitate further study of the formation of the supramolecular form(s) of A(type 2)-Ad-DE and other glycolipids within the glycocalyx and its further fate in new therapeutic strategies.