Insights into gliadin supramolecular organization at digestive pH 3.0

• Published in: Colloids and surfaces, B, Biointerfaces Vol. 165; pp. 363 - 370
• Main Authors: Herrera, M.G., Vazquez, D.S., Sreij, R., Drechsler, M., Hertle, Y., Hellweg, T., Dodero, V.I.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.05.2018
• Subjects: biomedical research; Celiac disease; colloids; electron microscopy; Gliadin; gluten; Gluten-related disorders; human diseases; hydrodynamics; light scattering; molecular dynamics; Molecular simulation; Oligomers; prediction; SAXS; solvents; wheat; Oligomers; Molecular simulation; Celiac disease; Gluten-related disorders; Gliadin; SAXS
• ISSN: 0927-7765; 1873-4367; 1873-4367
• DOI: 10.1016/j.colsurfb.2018.02.053

[Display omitted] •Gliadin is an immunogenic protein present in wheat gluten which is not fully degraded by humans.•At digestive pH, gliadin solution is composed of prolate ellipsoidal dimers, and oligomers.•A molecular understanding of oligomerization propensity is provided. Alpha-gliadin is a highly immunogenic protein from wheat, which is associated with many human diseases, like celiac disease and non-celiac gluten sensitivity. Because of that, gliadin solution is subject to intense biomedical research. However, the physicochemical nature of the employed gliadin solution at physiological pH is not understood. Herein, we present a supramolecular evaluation of the alpha-gliadin protein in water at pH 3.0 by dynamic light scattering (DLS), cryo-transmission electron microscopy (cryo-TEM) and small-angle-.X-ray scattering (SAXS). We report that at 0.5 wt% concentration (0.1 mg/ml), gliadin is already a colloidal polydisperse system with an average hydrodynamic radius of 30 ± 10 nm. By cryo-TEM, we detected mainly large clusters. However, it was possible to visualise for the first time prolate oligomers of around 68 nm and 103 nm, minor and major axis, respectively. SAXS experiments support the existence of prolate/rod-like structures. At 1.5 wt% concentration gliadin dimers, small oligomers and large clusters coexist. The radius of gyration (Rg1) of gliadin dimer is 5.72 ± 0.23 nm with a dimer cross-section (Rc) of 1.63 nm, and an average length of around 19 nm, this suggests that gliadin dimers are formed longitudinally. Finally, our alpha-gliadin 3D model, obtained by ab initio prediction and analysed by molecular dynamics (MD), predicts that two surfaces prone to aggregation are exposed to the solvent, at the C-terminus. We hypothesise that this region may be involved in the dimerisation process of alpha-gliadin.