Annual Review of Physical Chemistry Chemical Kinetics for Bridging Molecular Mechanisms and Macroscopic Measurements of Amyloid Fibril Formation Thomas C.T. Michaels, 1,2 An ¯ dela ˇ Sari´ c, 3 Johnny Habchi, 1 Sean Chia, 1 Georg Meisl, 1 Michele Vendruscolo, 1 Christopher M. Dobson, 1 and Tuomas P.J. Knowles 1,4 1 Centre for Misfolding Diseases, Department of Chemistry, University of Cambridge, Cambridge CB2 1EW, United Kingdom; email: tpjk2@cam.ac.uk 2 Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, Massachusetts 02138, USA 3 Department of Physics and Astronomy, and Institute for the Physics of Living Systems, University College London, London WC1E 6BT, United Kingdom 4 Cavendish Laboratory, Department of Physics, University of Cambridge, Cambridge CB3 1HE, United Kingdom; email: mv245@cam.ac.uk, cmd44@cam.ac.uk Annu. Rev. Phys. Chem. 2018. 69:273–98 First published as a Review in Advance on February 28, 2018 The Annual Review of Physical Chemistry is online at physchem.annualreviews.org https://doi.org/10.1146/annurev-physchem- 050317-021322 Copyright c  2018 by Annual Reviews. All rights reserved Keywords protein misfolding, protein aggregation, Alzheimer’s disease, neurodegenerative diseases, self-assembly, rate law, master equation, reaction order, scaling exponent, global fit, secondary nucleation, oligomers, inhibition, drug discovery, computer simulations, coarse-grained simulations Abstract Understanding how normally soluble peptides and proteins aggregate to form amyloid fibrils is central to many areas of modern biomolecular sci- ence, ranging from the development of functional biomaterials to the design of rational therapeutic strategies against increasingly prevalent medical con- ditions such as Alzheimer’s and Parkinson’s diseases. As such, there is a great need to develop models to mechanistically describe how amyloid fibrils are formed from precursor peptides and proteins. Here we review and discuss 273 Click here to view this article's online features: • Download figures as PPT slides • Navigate linked references • Download citations • Explore related articles • Search keywords ANNUAL REVIEWS Further Annu. Rev. Phys. Chem. 2018.69:273-298. Downloaded from www.annualreviews.org Access provided by Cambridge University on 04/22/18. For personal use only.