Review
FTIR spectroscopic imaging of protein aggregation in living cells

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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.

Graphical abstract

Highlights

► We review FTIR spectroscopy for evaluating the secondary structure of proteins. ► We describe its use for investigating protein misfolding and aggregation in vitro. ► New technology has enabled determination of aggregate structure in cells and tissue. ► Time-lapsed FTIR imaging of protein aggregation within living cells is demonstrated. ► Results can reveal the structural intermediates and mechanisms of cell toxicity.

Keywords

Fourier transform infrared (FTIR) spectroscopy
Microspectroscopy
Protein secondary structure
Protein aggregation
Amyloid

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This article is part of a Special Issue entitled: FTIR in membrane proteins and peptide studies.