FTIR spectroscopic imaging of protein aggregation in living cells

Biochim Biophys Acta. 2013 Oct;1828(10):2339-46. doi: 10.1016/j.bbamem.2013.01.014. Epub 2013 Jan 25.

Abstract

Protein misfolding and aggregation are the hallmark of a number of diseases including Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, and the prion diseases. In all cases, a naturally-occurring protein misfolds and forms aggregates that are thought to disrupt cell function through a wide range of mechanisms that are yet to be fully unraveled. Fourier transform infrared (FTIR) spectroscopy is a technique that is sensitive to the secondary structure of proteins and has been widely used to investigate the process of misfolding and aggregate formation. This review focuses on how FTIR spectroscopy and spectroscopic microscopy are being used to evaluate the structural changes in disease-related proteins both in vitro and directly within cells and tissues. Finally, ongoing technological advances will be presented that are enabling time-resolved FTIR imaging of protein aggregation directly within living cells, which can provide insight into the structural intermediates, time scale, and mechanisms of cell toxicity associated with aggregate formation. This article is part of a Special Issue entitled: FTIR in membrane proteins and peptide studies.

Keywords: Amyloid; Fourier transform infrared (FTIR) spectroscopy; Microspectroscopy; Protein aggregation; Protein secondary structure.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Humans
  • Neurodegenerative Diseases / metabolism
  • Neurodegenerative Diseases / pathology
  • Protein Conformation
  • Proteins / chemistry*
  • Spectroscopy, Fourier Transform Infrared / methods*

Substances

  • Proteins