title: Dimethyl Sulfoxide Induced Destabilization and Disassembly of Various Structural Variants of Insulin Fibrils Monitored by Vibrational Circular Dichroism.
abstract: Dimethyl sulfoxide (DMSO) induced destabilization of insulin fibrils has been previously studied by Fourier transform infrared spectroscopy and interpreted in terms of secondary structural changes. The variation of this process for fibrils with different types of higher-order morphological structures remained unclear. Here, we utilize vibrational circular dichroism (VCD), which has been reported to provide a useful biophysical probe of the supramolecular chirality of amyloid fibrils, to characterize changes in the macroscopic chirality following DMSO-induced disassembly for two types of insulin fibrils formed under different conditions, at different reduced pH values with and without added salt and agitation. We confirm that very high concentrations of DMSO can disaggregate both types of insulin fibrils, which initially maintained a β-sheet conformation and eventually changed their secondary structure to a disordered form. The two types responded to varying concentrations of DMSO, and disaggregation followed different mechanisms. Interconversion of specific insulin fibril morphological types also occurred during the destabilization process as monitored by VCD. With transmission electron microscopy, we were able to correlate the changes in VCD sign patterns to alteration of morphology of the insulin fibrils.
authors.affiliation: Department of Chemistry, University of Illinois at Chicago , 845 West Taylor Street (m/c 111), Chicago, Illinois 60607-7061, United States.
authors.forename: Ge
authors.initials: G
authors.lastname: Zhang
authors.affiliation: Department of Chemistry, Biological and Chemical Research Centre, University of Warsaw , Pasteura 1, 02-093 Warsaw, Poland.
authors.forename: Viktoria
authors.initials: V
authors.lastname: Babenko
authors.affiliation: Department of Chemistry, Biological and Chemical Research Centre, University of Warsaw , Pasteura 1, 02-093 Warsaw, Poland.
authors.forename: Wojciech
authors.initials: W
authors.lastname: Dzwolak
authors.affiliation: Department of Chemistry, University of Illinois at Chicago , 845 West Taylor Street (m/c 111), Chicago, Illinois 60607-7061, United States.
authors.forename: Timothy A
authors.initials: TA
authors.lastname: Keiderling
mesh_terms: D002942:Circular Dichroism; D004121:Dimethyl Sulfoxide / Q000737:chemistry*; D007328:Insulin / Q000737:chemistry*; D046912:Multiprotein Complexes / Q000737:chemistry* / Q000648:ultrastructure
chemical_list: D007328:Insulin; D046912:Multiprotein Complexes; D004121:Dimethyl Sulfoxide