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Atomic force microscopy for single molecule characterisation of protein aggregation.

Authors
  • Ruggeri, Francesco Simone1
  • Šneideris, Tomas2
  • Vendruscolo, Michele3
  • Knowles, Tuomas P J4
  • 1 Centre for Misfolding Disease, Department of Chemistry, University of Cambridge, Cambridge, CB2 1EW, United Kingdom. Electronic address: [email protected] , (United Kingdom)
  • 2 Centre for Misfolding Disease, Department of Chemistry, University of Cambridge, Cambridge, CB2 1EW, United Kingdom; Institute of Biotechnology, Life Sciences Center, Vilnius University, Vilnius, Lithuania. , (United Kingdom)
  • 3 Centre for Misfolding Disease, Department of Chemistry, University of Cambridge, Cambridge, CB2 1EW, United Kingdom. , (United Kingdom)
  • 4 Centre for Misfolding Disease, Department of Chemistry, University of Cambridge, Cambridge, CB2 1EW, United Kingdom; Cavendish Laboratory, University of Cambridge, Cambridge, CB3 0HE, United Kingdom. Electronic address: [email protected] , (United Kingdom)
Type
Published Article
Journal
Archives of Biochemistry and Biophysics
Publisher
Elsevier
Publication Date
Mar 30, 2019
Volume
664
Pages
134–148
Identifiers
DOI: 10.1016/j.abb.2019.02.001
PMID: 30742801
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

The development of atomic force microscopy (AFM) has opened up a wide range of novel opportunities in nanoscience and new modalities of observation in complex biological systems. AFM imaging has been widely employed to resolve the complex and heterogeneous conformational states involved in protein aggregation at the single molecule scale and shed light onto the molecular basis of a variety of human pathologies, including neurodegenerative disorders. The study of individual macromolecules at nanoscale, however, remains challenging, especially when fully quantitative information is required. In this review, we first discuss the principles of AFM with a special emphasis on the fundamental factors defining its sensitivity and accuracy. We then review the fundamental parameters and approaches to work at the limit of AFM resolution in order to perform single molecule statistical analysis of biomolecules and nanoscale protein aggregates. This single molecule statistical approach has proved to be powerful to unravel the molecular and hierarchical assembly of the misfolded species present transiently during protein aggregation, to visualise their dynamics at the nanoscale, as well to study the structural properties of amyloid-inspired functional nanomaterials. Copyright © 2019. Published by Elsevier Inc.

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