Two-dimensional infrared spectroscopy provides evidence of an intermediate in the membrane-catalyzed assembly of diabetic amyloid

Yun L. Ling, David B. Strasfeld, Sang-Hee Shim, Daniel P. Raleigh, Martin T. Zanni

Research output: Contribution to journalArticle

53 Citations (Scopus)

Abstract

Islet amyloid polypeptide (IAPP, also known as amylin) is responsible for pancreatic amyloid deposits in type 2 diabetes. The deposits, as well as intermediates in their assembly, are cytotoxic to pancreatic β-cells and contribute to the loss of β-cell mass associated with type 2 diabetes. The factors that trigger islet amyloid deposition in vivo are not well understood, but peptide membrane interactions have been postulated to play an important role in islet amyloid formation. To better understand the role of membrane interactions in amyloid formation, two-dimensional infrared (2D IR) spectroscopy was used to compare the kinetics of amyloid formation for human IAPP both in the presence and in the absence of negatively charged lipid vesicles. Comparison of spectral features and kinetic traces from the two sets of experiments provides evidence for the formation of an ordered intermediate during the membrane-mediated assembly of IAPP amyloid. A characteristic transient spectral feature is detected during amyloid formation in the presence of vesicles that is not observed in the absence of vesicles. The spectral feature associated with the intermediate raises in intensity during the self-assembly process and subsequently decays in intensity in the classic manner of a kinetic intermediate. Studies with rat IAPP, a variant that is known to interact with membranes but does not form amyloid, confirm the presence of an intermediate. The analysis of 2D IR spectra in terms of specific structural features is discussed. The unique combination of time and secondary structure resolution of 2D IR spectroscopy has enabled the time-evolution of a hIAPP intermediate to be directly monitored for the first time. The data presented here demonstrates the utility of 2D IR spectroscopy for studying membrane-catalyzed amyloid formation.

Original languageEnglish
Pages (from-to)2498-2505
Number of pages8
JournalJournal of Physical Chemistry B
Volume113
Issue number8
DOIs
Publication statusPublished - 2009 Feb 26
Externally publishedYes

Fingerprint

Amyloid
Infrared spectroscopy
Spectrum Analysis
assembly
infrared spectroscopy
membranes
Membranes
Islet Amyloid Polypeptide
kinetics
deposits
Type 2 Diabetes Mellitus
spectroscopy
Medical problems
Kinetics
polypeptides
Deposits
cells
rats
peptides
lipids

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Surfaces, Coatings and Films
  • Materials Chemistry

Cite this

Two-dimensional infrared spectroscopy provides evidence of an intermediate in the membrane-catalyzed assembly of diabetic amyloid. / Ling, Yun L.; Strasfeld, David B.; Shim, Sang-Hee; Raleigh, Daniel P.; Zanni, Martin T.

In: Journal of Physical Chemistry B, Vol. 113, No. 8, 26.02.2009, p. 2498-2505.

Research output: Contribution to journalArticle

Ling, Yun L. ; Strasfeld, David B. ; Shim, Sang-Hee ; Raleigh, Daniel P. ; Zanni, Martin T. / Two-dimensional infrared spectroscopy provides evidence of an intermediate in the membrane-catalyzed assembly of diabetic amyloid. In: Journal of Physical Chemistry B. 2009 ; Vol. 113, No. 8. pp. 2498-2505.
@article{f93a89eeb3324dffa821bf260f5dda9b,
title = "Two-dimensional infrared spectroscopy provides evidence of an intermediate in the membrane-catalyzed assembly of diabetic amyloid",
abstract = "Islet amyloid polypeptide (IAPP, also known as amylin) is responsible for pancreatic amyloid deposits in type 2 diabetes. The deposits, as well as intermediates in their assembly, are cytotoxic to pancreatic β-cells and contribute to the loss of β-cell mass associated with type 2 diabetes. The factors that trigger islet amyloid deposition in vivo are not well understood, but peptide membrane interactions have been postulated to play an important role in islet amyloid formation. To better understand the role of membrane interactions in amyloid formation, two-dimensional infrared (2D IR) spectroscopy was used to compare the kinetics of amyloid formation for human IAPP both in the presence and in the absence of negatively charged lipid vesicles. Comparison of spectral features and kinetic traces from the two sets of experiments provides evidence for the formation of an ordered intermediate during the membrane-mediated assembly of IAPP amyloid. A characteristic transient spectral feature is detected during amyloid formation in the presence of vesicles that is not observed in the absence of vesicles. The spectral feature associated with the intermediate raises in intensity during the self-assembly process and subsequently decays in intensity in the classic manner of a kinetic intermediate. Studies with rat IAPP, a variant that is known to interact with membranes but does not form amyloid, confirm the presence of an intermediate. The analysis of 2D IR spectra in terms of specific structural features is discussed. The unique combination of time and secondary structure resolution of 2D IR spectroscopy has enabled the time-evolution of a hIAPP intermediate to be directly monitored for the first time. The data presented here demonstrates the utility of 2D IR spectroscopy for studying membrane-catalyzed amyloid formation.",
author = "Ling, {Yun L.} and Strasfeld, {David B.} and Sang-Hee Shim and Raleigh, {Daniel P.} and Zanni, {Martin T.}",
year = "2009",
month = "2",
day = "26",
doi = "10.1021/jp810261x",
language = "English",
volume = "113",
pages = "2498--2505",
journal = "Journal of Physical Chemistry B Materials",
issn = "1520-6106",
publisher = "American Chemical Society",
number = "8",

}

TY - JOUR

T1 - Two-dimensional infrared spectroscopy provides evidence of an intermediate in the membrane-catalyzed assembly of diabetic amyloid

AU - Ling, Yun L.

AU - Strasfeld, David B.

AU - Shim, Sang-Hee

AU - Raleigh, Daniel P.

AU - Zanni, Martin T.

PY - 2009/2/26

Y1 - 2009/2/26

N2 - Islet amyloid polypeptide (IAPP, also known as amylin) is responsible for pancreatic amyloid deposits in type 2 diabetes. The deposits, as well as intermediates in their assembly, are cytotoxic to pancreatic β-cells and contribute to the loss of β-cell mass associated with type 2 diabetes. The factors that trigger islet amyloid deposition in vivo are not well understood, but peptide membrane interactions have been postulated to play an important role in islet amyloid formation. To better understand the role of membrane interactions in amyloid formation, two-dimensional infrared (2D IR) spectroscopy was used to compare the kinetics of amyloid formation for human IAPP both in the presence and in the absence of negatively charged lipid vesicles. Comparison of spectral features and kinetic traces from the two sets of experiments provides evidence for the formation of an ordered intermediate during the membrane-mediated assembly of IAPP amyloid. A characteristic transient spectral feature is detected during amyloid formation in the presence of vesicles that is not observed in the absence of vesicles. The spectral feature associated with the intermediate raises in intensity during the self-assembly process and subsequently decays in intensity in the classic manner of a kinetic intermediate. Studies with rat IAPP, a variant that is known to interact with membranes but does not form amyloid, confirm the presence of an intermediate. The analysis of 2D IR spectra in terms of specific structural features is discussed. The unique combination of time and secondary structure resolution of 2D IR spectroscopy has enabled the time-evolution of a hIAPP intermediate to be directly monitored for the first time. The data presented here demonstrates the utility of 2D IR spectroscopy for studying membrane-catalyzed amyloid formation.

AB - Islet amyloid polypeptide (IAPP, also known as amylin) is responsible for pancreatic amyloid deposits in type 2 diabetes. The deposits, as well as intermediates in their assembly, are cytotoxic to pancreatic β-cells and contribute to the loss of β-cell mass associated with type 2 diabetes. The factors that trigger islet amyloid deposition in vivo are not well understood, but peptide membrane interactions have been postulated to play an important role in islet amyloid formation. To better understand the role of membrane interactions in amyloid formation, two-dimensional infrared (2D IR) spectroscopy was used to compare the kinetics of amyloid formation for human IAPP both in the presence and in the absence of negatively charged lipid vesicles. Comparison of spectral features and kinetic traces from the two sets of experiments provides evidence for the formation of an ordered intermediate during the membrane-mediated assembly of IAPP amyloid. A characteristic transient spectral feature is detected during amyloid formation in the presence of vesicles that is not observed in the absence of vesicles. The spectral feature associated with the intermediate raises in intensity during the self-assembly process and subsequently decays in intensity in the classic manner of a kinetic intermediate. Studies with rat IAPP, a variant that is known to interact with membranes but does not form amyloid, confirm the presence of an intermediate. The analysis of 2D IR spectra in terms of specific structural features is discussed. The unique combination of time and secondary structure resolution of 2D IR spectroscopy has enabled the time-evolution of a hIAPP intermediate to be directly monitored for the first time. The data presented here demonstrates the utility of 2D IR spectroscopy for studying membrane-catalyzed amyloid formation.

UR - http://www.scopus.com/inward/record.url?scp=65249173508&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=65249173508&partnerID=8YFLogxK

U2 - 10.1021/jp810261x

DO - 10.1021/jp810261x

M3 - Article

VL - 113

SP - 2498

EP - 2505

JO - Journal of Physical Chemistry B Materials

JF - Journal of Physical Chemistry B Materials

SN - 1520-6106

IS - 8

ER -