Understanding the structural differences between spherical and rod-shaped human insulin nanoparticles produced by supercritical fluids precipitation.

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.

Conformational Effects in the Transport of Glucose through a Cyclic Peptide Nanotube: A Molecular Dynamics Simulation Study.

The transport behavior of glucose through a cyclic peptide nanotube (CPN), composed of 8 × cyclo[-(Trp-d-Leu)4-Gln-d-Leu-] rings embedded in DMPC lipid bilayers was examined using all-atom molecular dynamics (AAMD) simulations. Two conformational isomers of ß-d-glucose, equatorial (4C1) and axial (1C4) chair conformers, were used to examine conformational effects on the hydrogen bond network, energetics, and diffusivity of glucose transport through the CPN. Calculations of the number of hydrogen bonds of the two glucose conformers with water molecules and with the CPN illustrate that the total number of hydrogen bonds of the conformers decreases inside the channel compared to bulk water due to the confinement characteristics of the interior of the CPNs although new hydrogen bonds between the hydroxyl and hydroxymethyl hydrogens of glucose and the carbonyl oxygens in the CPN backbone are formed. Despite the decrease of the number of hydrogen bonds inside the CPN, intramolecular hydrogen bonds of 1C4 are maintained during permeation of 1C4 through the CPN. The retention of intramolecular hydrogen bonds and the spherical shape of 1C4 give rise to considerably weaker orientational preferences and higher diffusion coefficients for 1C4 than those of 4C1 inside and outside the CPN. Due to larger dipole moments induced by the alignment of hydroxyl and hydroxymethyl groups, 1C4 has more favorable interactions with the CPN backbone at the channel entrances and inside the channel than 4C1. In the middle of the CPN channel, entropic gains originating from higher orientational and translational degrees of freedom of 1C4 than those of 4C1 also contribute to lower free energy wells for 1C4 inside the CPN. This work reveals that the conformational variation and intramolecular hydrogen bond formation of ß-d-glucose can have important effects on the energetics and dynamics of glucose transport through CPNs, providing insight into the translocation mechanism of d-glucose into the cell through glucose transporters (GLUTs) and the dynamics of glucose confined in silica nanochannels. It is also demonstrated that CPNs can indeed facilitate the permeation of small hydrophilic molecules such as glucose and can be utilized as a novel carrier system for hydrophilic drug compounds into the cell.