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Biophysical Reviews

, Volume 11, Issue 2, pp 191–208 | Cite as

Unified theoretical description of the kinetics of protein aggregation

  • Nami Hirota
  • Herman Edskes
  • Damien HallEmail author
Review

Abstract

Solution conditions chosen for the production of amyloid can also promote formation of significant extents of amorphous protein aggregate. In one interpretation, the amyloid and amorphous aggregation pathways are considered to be in competition with each other. An alternative conceptualization involves considering amorphous aggregation as an obligatory intermediate process of the amyloid formation pathway. Here, we review recently developed macroscopic-level theories of protein aggregation that unify these two competing models into a single paradigm. Key features of the unified model included (1) a description of the amorphous aggregate as a second liquid phase with the degree of liquid-like character determined by the mobility of the monomer within it, and (2) heterogeneous growth pathways based on nucleation, growth, and fragmentation of amyloid occurring within different phases and at their interfacial boundary. Limiting-case behaviors of the protein aggregation reaction, either singly involving amyloid or amorphous aggregate production, and mixed-case behaviors, involving competitive and/or facilitated growth of amorphous and amyloid species, are presented and reviewed in context. This review principally describes an approach developed by Hirota and Hall 2019 (Hirota, N. and Hall, D. 2019. Protein Aggregation Kinetics: A Unified Theoretical Description. Chapter 7 of ‘Protein Solubility and Amorphous Aggregation: From Academic Research to Applications in Drug Discovery and Bioindustry’ edited by Y. Kuroda and F. Arisaka. CMC Publishers). Sections of that work are translated from the original Japanese and republished here with the full permission of CMC Publishing Corporation.

Keywords

Kinetics Protein aggregation Amyloid United model 

Notes

Acknowledgements

NH would like to thank supporting funds from Do International Trading House. HE: This research was supported, in part, by the Intramural Research Program of the NIH, The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). Initial and later aspects of the work of DH were respectively supported by funds and resources associated with an Australian National University (ANU) Senior Research Fellowship and an Associate Professorship at the Institute for Protein Research, Osaka University. DH would also like to express thanks to The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) for financial support in the form of a two-month visiting fellowship in July and August of 2018.

Compliance with ethical standards

Conflict of interest

Nami Hirota declares that she has no conflict of interest. Herman Edskes declares that he has no conflict of interest. Damien Hall declares that he has no conflict of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

References

  1. Auer S, Meersman F, Dobson CM, Vendruscolo M (2008) A generic mechanism of emergence of amyloid protofilaments from disordered oligomeric aggregates. PLoS Comput Biol 4(11):e1000222Google Scholar
  2. Auer S, Ricchiuto P, Kashchiev D (2012) Two-step nucleation of amyloid fibrils: omnipresent or not? J Mol Biol 422(5):723–730Google Scholar
  3. Baldwin RL (1996) On-pathway versus off-pathway folding intermediates. Fold Des 1(1):R1–R8Google Scholar
  4. Ban T, Goto Y (2006) Direct observation of amyloid growth monitored by total internal reflection fluorescence microscopy. Methods in enzymology 413:91–102Google Scholar
  5. Bennett CH (1972) Serially deposited amorphous aggregates of hard spheres. J Appl Phys 43:2727–2734Google Scholar
  6. Bentea L, Watzky MA, Finke RG (2017) Sigmoidal nucleation and growth curves across nature fit by the Finke–Watzky model of slow continuous nucleation and autocatalytic growth: explicit formulas for the lag and growth times plus other key insights. J Phys Chem C 121(9):5302–5312Google Scholar
  7. Binger KJ, Pham CL, Wilson LM, Bailey MF, Lawrence LJ, Schuck P, Howlett GJ (2008) Apolipoprotein C-II amyloid fibrils assemble via a reversible pathway that includes fibril breaking and rejoining. J Mol Biol 376(4):1116–1129Google Scholar
  8. Carulla N, Caddy GL, Hall DR, Zurdo J, Gairí M, Feliz M, Giralt E, Robinson CV, Dobson CM (2005) Molecular recycling within amyloid fibrils. Nature 436(7050):554Google Scholar
  9. Cheon M, Chang I, Mohanty S, Luheshi LM, Dobson CM, Vendruscolo M, Favrin G (2007) Structural reorganisation and potential toxicity of oligomeric species formed during the assembly of amyloid fibrils. PLoS Comput Biol 3(9):e173Google Scholar
  10. Dill KA, Chan HS (1997) From Levinthal to pathways to funnels. Nat Struct Mol Biol 4(1):10Google Scholar
  11. Dorta-Estremera SM, Li J, Cao W (2013) Rapid generation of amyloid from native proteins in vitro. J Vis Exp 82:50869Google Scholar
  12. DuBay KF, Pawar AP, Chiti F, Zurdo J, Dobson CM, Vendruscolo M (2004) Prediction of the absolute aggregation rates of amyloidogenic polypeptide chains. J Mol Biol 341(5):1317–1326Google Scholar
  13. Edskes HK, Kryndushkin D, Shewmaker F, Wickner RB (2017) Prion transfection of yeast. Cold Spring Harb Protoc 2017(2):112–117Google Scholar
  14. Eisenberg DS, Sawaya MR (2017) Structural studies of amyloid proteins at the molecular level. Annu Rev Biochem 86:69–95Google Scholar
  15. Fink AL (1998) Protein aggregation: folding aggregates, inclusion bodies and amyloid. Fold Des 3(1):R9–R23Google Scholar
  16. Fodera V, Librizzi F, Groenning M, Van De Weert M, Leone M (2008) Secondary nucleation and accessible surface in insulin amyloid fibril formation. J Phys Chem B 112(12):3853–3858Google Scholar
  17. Friedlander SK, Smoke D (2000) Haze: fundamentals of aerosol dynamics. Oxford University Press, New YorkGoogle Scholar
  18. Gillespie T, Rideal EK (1956) The coalescence of drops at an oil-water interface. Trans Faraday Soc 52:173–183Google Scholar
  19. Goldschmidt L, Teng PK, Riek R, Eisenberg D (2010) Identifying the amylome, proteins capable of forming amyloid-like fibrils. Proc Natl Acad Sci 107(8):3487–3492Google Scholar
  20. Grigolato F, Colombo C, Ferrari R, Rezabkova L, Arosio P (2017) Mechanistic origin of the combined effect of surfaces and mechanical agitation on amyloid formation. ACS Nano 11(11):11358–11367Google Scholar
  21. Hall D (2001) Use of optical biosensors for the study of mechanistically concerted surface adsorption processes. Anal Biochem 288(2):109–125Google Scholar
  22. Hall D (2008) Kinetic models describing biomolecular interactions at surfaces. In: Handbook of Surface Plasmon Resonance. Royal Society of Chemistry, pp 81–122Google Scholar
  23. Hall D (2012) Semi-automated methods for simulation and measurement of amyloid fiber distributions obtained from transmission electron microscopy experiments. Anal Biochem 421(1):262–277Google Scholar
  24. Hall D (2017) A composite polynomial approach for analyzing the indefinite self-association of macromolecules studied by sedimentation equilibrium. Biophys Chem 228:10–16Google Scholar
  25. Hall D, Edskes H (2004) Silent prions lying in wait: a two-hit model of prion/amyloid formation and infection. J Mol Biol 336(3):775–786Google Scholar
  26. Hall D, Edskes H (2012) Computational modeling of the relationship between amyloid and disease. Biophys Rev 4(3):205–222Google Scholar
  27. Hall D, Hirota N (2009) Multi-scale modelling of amyloid formation from unfolded proteins using a set of theory derived rate constants. Biophys Chem 140(1–3):122–128Google Scholar
  28. Hall D, Hoshino M 2010 Effects of macromolecular crowding on intracellular diffusion from a single particle perspective. Biophysical reviews, 2(1):39–53Google Scholar
  29. Hall D, Huang L (2012) On the use of size-exclusion chromatography for the resolution of mixed amyloid-aggregate distributions (I). Anal Biochem 426:69–85Google Scholar
  30. Hall D, Minton AP (2002) Effects of inert volume-excluding macromolecules on protein fiber formation. I. Equilibrium models. Biophys Chem 98(1–2):93–104Google Scholar
  31. Hall D, Minton AP (2004) Effects of inert volume-excluding macromolecules on protein fiber formation. II. Kinetic models for nucleated fiber growth. Biophys Chem 107(3):299–316Google Scholar
  32. Hall D, Hirota N, Dobson CM (2005) A toy model for predicting the rate of amyloid formation from unfolded protein. J Mol Biol 351(1):195–205Google Scholar
  33. Hall D, Kardos J, Edskes H, Carver JA, Goto Y (2015) A multi-pathway perspective on protein aggregation: implications for control of the rate and extent of amyloid formation. FEBS Lett 589(6):672–679Google Scholar
  34. Hall D, Zhao R, So M, Adachi M, Rivas G, Carver JA, Goto Y (2016) Recognizing and analyzing variability in amyloid formation kinetics. Anal Biochem 510:56–71Google Scholar
  35. Hall D, Kinjo A, Goto Y (2018) A new look at an old view of denaturant induced protein unfolding. Anal Biochem 542:40–57Google Scholar
  36. Hirota N, Hall D (2019) Protein aggregation kinetics: a unified theoretical description. In: Kuroda Y, Arisaka F (eds) Chapter 7 of ‘Protein Solubility and Amorphous Aggregation: From Academic Research to Applications in Drug Discovery and Bioindustry’. CMC Publishers, Tokyo (original article in Japanese)Google Scholar
  37. Kim PS, Baldwin RL (1982) Specific intermediates in the folding reactions of small proteins and the mechanism of protein folding. Annu Rev Biochem 51(1):459–489Google Scholar
  38. Kryndushkin D, Edskes HK, Shewmaker FP, Wickner RB (2017) Prions. Cold Spring Harbor Protocols, 2017(2), pp.pdb-top077586Google Scholar
  39. Kuwajima K, Yamaya H, Miwa S, Sugai S, Nagamura T (1987) Rapid formation of secondary structure framework in protein folding studied by stopped‐flow circular dichroism. FEBS letters. 221(1):115–118Google Scholar
  40. Lansbury PT (1999) Evolution of amyloid: what normal protein folding may tell us about fibrillogenesis and disease. Proc Natl Acad Sci 96(7):3342–3344Google Scholar
  41. Linse S, Cabaleiro-Lago C, Xue WF, Lynch I, Lindman S, Thulin E, Radford SE, Dawson KA (2007) Nucleation of protein fibrillation by nanoparticles. Proc Natl Acad Sci 104(21):8691–8696Google Scholar
  42. Lomakin A, Chung DS, Benedek GB, Kirschner DA, Teplow DB (1996) On the nucleation and growth of amyloid beta-protein fibrils: detection of nuclei and quantitation of rate constants. Proc Natl Acad Sci 93(3):1125–1129Google Scholar
  43. Lumry R, Eyring H (1954) Conformational changes of proteins. J Phys Chem 58:110–120Google Scholar
  44. Masel J, Jansen VA, Nowak MA (1999) Quantifying the kinetic parameters of prion replication. Biophys Chem 77(2–3):139–152Google Scholar
  45. Mezzenga R, Fischer P (2013) The self-assembly, aggregation and phase transitions of food protein systems in one, two and three dimensions. Rep Prog Phys 76(4):046601Google Scholar
  46. Michnick SW, Bergeron-Sandoval LP (2018) Why does biopolymer condensation matter? Nat Rev Mol Cell Biol 19(1):613–614Google Scholar
  47. Nayak A, Dutta AK, Belfort G (2008) Surface-enhanced nucleation of insulin amyloid fibrillation. Biochem Biophys Res Commun 369(2):303–307Google Scholar
  48. Nguyen HD, Hall CK (2004) Molecular dynamics simulations of spontaneous fibril formation by random-coil peptides. Proc Natl Acad Sci 101(46):16180–16185Google Scholar
  49. Nilsson MR (2004) Techniques to study amyloid fibril formation in vitro. Methods 34(1):151–160Google Scholar
  50. Oosawa F, Asakura S (1975) Thermodynamics of the polymerization of protein. London. Academic Press, New YorkGoogle Scholar
  51. Oosawa F, Kasai M (1962) A theory of linear and helical aggregations of macromolecules. J Mol Biol 4(1):10–21Google Scholar
  52. Oxtoby DW (1992) Homogeneous nucleation: theory and experiment. J Phys Condens Matter 4(38):7627Google Scholar
  53. Pallitto MM, Murphy RM (2001) A mathematical model of the kinetics of β-amyloid fibril growth from the denatured state. Biophys J 81(3):1805–1822Google Scholar
  54. Qin Z, Hu D, Zhu M, Fink AL (2007) Structural characterization of the partially folded intermediates of an immunoglobulin light chain leading to amyloid fibrillation and amorphous aggregation. Biochemistry 46(11):3521–3531Google Scholar
  55. Schreck JS, Yuan JM (2013) A kinetic study of amyloid formation: fibril growth and length distributions. J Phys Chem B 117(21):6574–6583Google Scholar
  56. Shin Y, Brangwynne CP (2017) Liquid phase condensation in cell physiology and disease. Science 357(6357):eaaf4382Google Scholar
  57. Thakur G, Micic M, Leblanc RM (2009) Surface chemistry of Alzheimer’s disease: a Langmuir monolayer approach. Colloids Surf B: Biointerfaces 74(2):436–456Google Scholar
  58. Tohver V, Smay JE, Braem A, Braun PV, Lewis JA (2001) Nanoparticle halos: a new colloid stabilization mechanism. Proc Natl Acad Sci 98(16):8950–8954Google Scholar
  59. Tsai DH, Pease LF III, Zangmeister RA, Tarlov MJ, Zachariah MR (2008) Aggregation kinetics of colloidal particles measured by gas-phase differential mobility analysis. Langmuir 25(1):140–146Google Scholar
  60. Tycko R, Wickner RB (2013) Molecular structures of amyloid and prion fibrils: consensus versus controversy. Acc Chem Res 46(7):1487–1496Google Scholar
  61. Usov I, Mezzenga R (2015) FiberApp: an open-source software for tracking and analyzing polymers, filaments, biomacromolecules, and fibrous objects. Macromolecules 48(5):1269–1280Google Scholar
  62. Vetri V, Canale C, Relini A, Librizzi F, Militello V, Gliozzi A, Leone M (2007) Amyloid fibrils formation and amorphous aggregation in concanavalin A. Biophys Chem 125(1):184–190Google Scholar
  63. von Smoluchowski M (1917) Versuch einer mathematischen Theorie der Koagulationskinetik kolloider Lösungen. Z Phys Chem 92:129Google Scholar
  64. Weber SC, Brangwynne CP (2012) Getting RNA and protein in phase. Cell 149(6):1188–1191Google Scholar
  65. Wickner RB, Shewmaker FP, Bateman DA, Edskes HK, Gorkovskiy A, Dayani Y, Bezsonov EE (2015) Yeast prions: structure, biology, and prion-handling systems. Microbiol Mol Biol Rev 79(1):1–17Google Scholar
  66. Wu C, Shea JE (2011) Coarse-grained models for protein aggregation. Curr Opin Struct Biol 21(2):209–220Google Scholar
  67. Xue WF, Homans SW, Radford SE (2008) Systematic analysis of nucleation-dependent polymerization reveals new insights into the mechanism of amyloid self-assembly. Proc Natl Acad Sci 105(26):8926–8931Google Scholar
  68. Zhao R, So M, Maat H, Ray NJ, Arisaka F, Goto Y, Carver JA, Hall D (2016) Measurement of amyloid formation by turbidity assay—seeing through the cloud. Biophys Rev 8(4):445–471Google Scholar
  69. Zhu M, Souillac PO, Ionescu-Zanetti C, Carter SA, Fink AL (2002) Surface-catalyzed amyloid fibril formation. J Biol Chem 277(52):50914–50922Google Scholar

Copyright information

© International Union for Pure and Applied Biophysics (IUPAB) and Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Do International Trading HouseNishinomiyaJapan
  2. 2.Laboratory of Biochemistry and GeneticsNIDDK, NIHBethesdaUSA
  3. 3.Institute for Protein ResearchOsaka UniversityOsakaJapan

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