Assays for Light Chain Amyloidosis Formation and Cytotoxicity

Methods Mol Biol. 2019:1873:123-153. doi: 10.1007/978-1-4939-8820-4_8.

Abstract

Common biophysical techniques like absorption and fluorescence spectroscopy, microscopy, and light scattering studies have been in use to investigate fibril assembly for a long time. However, there is sometimes a lack of consensus from the findings of an individual technique when compared in parallel with the other techniques. In this chapter, we aim to provide a concise compilation of techniques that can effectively be used to obtain a comprehensive representation of the structural, aggregation, and toxicity determinants in immunoglobulin light chain amyloidosis. We start by giving a brief introduction on amyloid assembly and the advantages of using simple and readily available techniques to study aggregation. After an overview on preparation of protein to set up parallel experiments, we provide a systematic description of the in vitro techniques used to study aggregation in AL protein. Additionally, we thoroughly discuss the steps needed in our experience during the individual experiments for better reproducibility and data analysis.

Keywords: Amyloid formation; Amyloidosis; Caspase assay; Cell viability; Electron microscopy; Immunoglobulin light chain; Sedimentation assay; Thioflavin T.

Publication types

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

MeSH terms

  • Amyloid / chemistry*
  • Amyloid / metabolism
  • Amyloidogenic Proteins / chemistry
  • Amyloidogenic Proteins / metabolism
  • Amyloidosis / diagnosis
  • Apoptosis
  • Benzothiazoles / chemistry
  • Benzothiazoles / metabolism
  • Biological Assay* / methods
  • Chromatography, Gel
  • Chromatography, High Pressure Liquid
  • Circular Dichroism
  • Dynamic Light Scattering
  • Immunoglobulin Light Chains / chemistry*
  • Immunoglobulin Light Chains / metabolism
  • Particle Size
  • Spectrometry, Fluorescence

Substances

  • Amyloid
  • Amyloidogenic Proteins
  • Benzothiazoles
  • Immunoglobulin Light Chains
  • thioflavin T