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Dynamics and Control of Peptide Self-Assembly and Aggregation

  • Georg MeislEmail author
  • Thomas C. T. Michaels
  • Paolo Arosio
  • Michele Vendruscolo
  • Christopher M. Dobson
  • Tuomas P. J. Knowles
Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1174)

Abstract

The aggregation of proteins into fibrillar structures is a central process implicated in the onset and development of several devastating neuro-degenerative diseases, but can, in contrast to these pathological roles, also fulfil important biological functions. In both scenarios, an understanding of the mechanisms by which soluble proteins convert to their fibrillar forms represents a fundamental objective for molecular sciences. This chapter details the different classes of microscopic processes responsible for this conversion and discusses how they can be described by a mathematical formulation of the aggregation kinetics. We present easily accessible experimental quantities that allow the determination of the dominant pathways of aggregation, as well as a general strategy to obtain detailed solutions to the kinetic rate laws that yield the microscopic rate constants of the individual processes of nucleation and growth. This chapter discusses a framework for a structured approach to address key questions regarding the dynamics of protein aggregation and shows how the use of chemical kinetics to tackle complex biophysical systems can lead to a deeper understanding of the underlying physical and chemical principles.

Keywords

Chemical kinetics Aggregation mechanisms Scaling exponent Global analysis 

Notes

Acknowledgements

We would like to thank the Swiss National Science Foundation, Peterhouse College Cambridge, the European Research Council, the BBSRC, the EPSRC, the Newman Foundation and Sidney Sussex College Cambridge.

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Copyright information

© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  • Georg Meisl
    • 1
    Email author
  • Thomas C. T. Michaels
    • 1
  • Paolo Arosio
    • 2
  • Michele Vendruscolo
    • 1
  • Christopher M. Dobson
    • 1
  • Tuomas P. J. Knowles
    • 3
    • 4
  1. 1.Department of ChemistryUniversity of CambridgeCambridgeUK
  2. 2.Department of Chemistry and Applied BioscienceETH ZurichZurichSwitzerland
  3. 3.Centre for Misfolding Diseases, Department of ChemistryUniversity of CambridgeCambridgeUK
  4. 4.Cavendish LaboratoryUniversity of CambridgeCambridgeUK

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