title: The role of glycerol and phosphatidylcholine in solubilizing and enhancing insulin stability in reverse hexagonal mesophases.
abstract: The potential of reverse hexagonal mesophases based on monoolein (GMO) and glycerol (as cosolvent) to facilitate the solubilization of proteins, such as insulin was explored. H(II) mesophases composed of GMO/decane/water were compared to GMO/decane/glycerol/water and GMO/phosphatidylcholine (PC)/decane/glycerol/water systems. The stability of insulin was tested, applying external physical modifications such as low pH and heat treatment (up to 70°C), in which insulin is known to form ordered amyloid-like aggregates (that are associated with several neurodegenerative diseases) with a characteristic cross β-pleated sheet structure. The impact of insulin confinement within these carriers on its stability, unfolding, and aggregation pathways was studied by combining SAXS, FTIR, and AFM techniques. These techniques provided a better insight into the molecular level of the "component interplay" in solubilizing and stabilizing insulin and its conformational modifications that dictate its final aggregate morphology. PC enlarged the water channels while glycerol shrank them, yet both facilitated insulin solubilization within the channels. The presence of glycerol within the mesophase water channels led to the formation of stronger hydrogen bonds with the hosting medium that enhanced the thermal stability of the protein and remarkably affected the unfolding process even after heat treatment (at 70°C for 60 min).
authors.affiliation: Casali Institute of Applied Chemistry, The Hebrew University of Jerusalem, Jerusalem 91904, Israel.
authors.forename: Idit
authors.initials: I
authors.lastname: Amar-Yuli
authors.forename: Doron
authors.initials: D
authors.lastname: Azulay
authors.forename: Tehila
authors.initials: T
authors.lastname: Mishraki
authors.forename: Abraham
authors.initials: A
authors.lastname: Aserin
authors.forename: Nissim
authors.initials: N
authors.lastname: Garti
mesh_terms: D005990:Glycerol / Q000737:chemistry*; D007328:Insulin / Q000737:chemistry*; D018625:Microscopy, Atomic Force; D010713:Phosphatidylcholines / Q000737:chemistry*; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared
chemical_list: D007328:Insulin; D010713:Phosphatidylcholines; D005990:Glycerol