title: New Insights from Sum Frequency Generation Vibrational Spectroscopy into the Interactions of Islet Amyloid Polypeptides with Lipid Membranes.
abstract: Studies of amyloid polypeptides on membrane surfaces have gained increasing attention in recent years. Several studies have revealed that membranes can catalyze protein aggregation and that the early products of amyloid aggregation can disrupt membrane integrity, increasing water permeability and inducing ion cytotoxicity. Nonetheless, probing aggregation of amyloid proteins on membrane surfaces is challenging. Surface-specific methods are required to discriminate contributions of aggregates at the membrane interface from those in the bulk phase and to characterize protein secondary structures in situ and in real time without the use of perturbing spectroscopic labels. Here, we review the most recent applications of sum frequency generation (SFG) vibrational spectroscopy applied in conjunction with computational modeling techniques, a joint experimental and computational methodology that has provided valuable insights into the aggregation of islet amyloid polypeptide (IAPP) on membrane surfaces. These applications show that SFG can provide detailed information about structures, kinetics, and orientation of IAPP during interfacial aggregation, relevant to the molecular mechanisms of type II diabetes. These recent advances demonstrate the promise of SFG as a new approach for studying amyloid diseases at the molecular level and for the rational drug design targeting early aggregation products on membrane surfaces.
authors.affiliation: William R. Wiley Environmental Molecular Sciences Laboratory, Pacific Northwest National Laboratory, P.O. Box 999, Richland, WA 99352, USA.
authors.forename: Li
authors.identifier: 0000-0003-0994-7789
authors.initials: L
authors.lastname: Fu
authors.affiliation: Department of Chemistry, Yale University, 225 Prospect Street, New Haven, CT 06520, USA.
authors.forename: Zhuguang
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Chemistry, Yale University, 225 Prospect Street, New Haven, CT 06520, USA.
authors.forename: Victor S
authors.initials: VS
authors.lastname: Batista
authors.affiliation: Department of Chemistry, Yale University, 225 Prospect Street, New Haven, CT 06520, USA.
authors.forename: Elsa C Y
authors.initials: EC
authors.lastname: Yan
mesh_terms: D002462:Cell Membrane / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D006801:Humans; D058228:Islet Amyloid Polypeptide / Q000378:metabolism*; D017433:Protein Structure, Secondary; D013057:Spectrum Analysis / Q000379:methods*
chemical_list: D058228:Islet Amyloid Polypeptide