title: Understanding the structural differences between spherical and rod-shaped human insulin nanoparticles produced by supercritical fluids precipitation.
abstract: In this study, the thermal denaturation mechanism and secondary structures of two types of human insulin nanoparticles produced by a process of solution-enhanced dispersion by supercritical fluids using dimethyl sulfoxide (DMSO) and ethanol (EtOH) solutions of insulin are investigated using spectroscopic approaches and molecular dynamics calculations. First, the temperature-dependent IR spectra of spherical and rod-shaped insulin nanoparticles prepared from DMSO and EtOH solution, respectively, are analyzed using principal component analysis (PCA) and 2D correlation spectroscopy to obtain a deeper understanding of the molecular structures and thermal behavior of the two insulin particle shapes. All-atom molecular dynamics (AAMD) calculations are performed to investigate the influence of the solvent molecules on the production of the insulin nanoparticles and to elucidate the geometric differences between the two types of nanoparticles. The results of the PCA, the 2D correlation spectroscopic analysis, and the AAMD calculations clearly reveal that the thermal denaturation mechanisms and the degrees of hydrogen bonding in the spherical and rod-shaped insulin nanoparticles are different. The polarity of the solvent might not alter the structure or function of the insulin produced, but the solvent polarity does influence the synthesis of different shapes of insulin nanoparticles.
authors.affiliation: Department of Chemistry and Institute for Molecular Science and Fusion Technology, Kangwon National University, Chuncheon 200-701 (Korea).
authors.forename: Yeonju
authors.initials: Y
authors.lastname: Park
authors.forename: Yongil
authors.initials: Y
authors.lastname: Seo
authors.forename: Boknam
authors.initials: B
authors.lastname: Chae
authors.forename: Dongjin
authors.initials: D
authors.lastname: Pyo
authors.forename: Hoeil
authors.initials: H
authors.lastname: Chung
authors.forename: Hyonseok
authors.initials: H
authors.lastname: Hwang
authors.forename: Young Mee
authors.initials: YM
authors.lastname: Jung
mesh_terms: D004121:Dimethyl Sulfoxide / Q000737:chemistry; D000431:Ethanol / Q000737:chemistry; D006801:Humans; D007328:Insulin / Q000737:chemistry* / Q000378:metabolism; D056004:Molecular Dynamics Simulation; D053758:Nanoparticles / Q000737:chemistry*; D025341:Principal Component Analysis; D013055:Spectrophotometry, Infrared; D013696:Temperature
chemical_list: D007328:Insulin; D000431:Ethanol; D004121:Dimethyl Sulfoxide
keywords: 2D correlation spectroscopy; insulin nanoparticles; molecular dynamics simulation; protein structure; solution-enhanced dispersion by supercritical fluids process