Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

Estimation of the lag time in a subsequent monomer addition model for fibril elongation

Suzanne K. Shoffner, View ORCID ProfileSantiago Schnell
doi: https://doi.org/10.1101/034900
Suzanne K. Shoffner
aDepartment of Molecular & Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Santiago Schnell
aDepartment of Molecular & Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
bDepartment of Computational Medicine and Bioinformatics, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
cBrehm Center for Diabetes Research, University of Michigan Medical School, Ann Arbor, MI 48105, USA.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Santiago Schnell
  • For correspondence: schnells@umich.edu
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Supplementary material
  • Preview PDF
Loading

Abstract

Fibrillogenesis, the production or development of protein fibers, has been linked to protein folding diseases. The progress curve of fibrils or aggregates typically takes on a sigmoidal shape witha lag phase, a rapid growth phase, and a final plateau regime. The study of the lag phase and the estimation of its critical timescale provide insight into the factors regulating the fibrillation process. However, methods to estimate a quantitative expression for the lag time rely on empirical expressions, which cannot connect the lag time to kinetic parameters associated with the reaction mechanisms of protein fibrillation. Here we introduce an approach for the estimation of the lag time using the governing rate equations of the elementary reactions of a subsequent monomer addition model for protein fibrillation as a case study. We show that the lag time is given by the sum of the critical timescales for each fibril intermediate in the subsequent monomer addition mechanism and therefore reveals causal connectivity between intermediate species. Furthermore, we find that single-molecule assays of protein fibrillation can exhibit a lag phase without a nucleation process, while dyes and extrinsic fluorescent probe bulk assays of protein fibrillation do not exhibit an observable lag time phase during template-dependent elongation. Our approach could be valuable for investigating the effects of intrinsic and extrinsic factors to the protein fibrillation reaction mechanism and provides physicochemical insights into parameters regulating the lag phase.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license.
Back to top
PreviousNext
Posted April 22, 2016.
Download PDF

Supplementary Material

Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
Estimation of the lag time in a subsequent monomer addition model for fibril elongation
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
Estimation of the lag time in a subsequent monomer addition model for fibril elongation
Suzanne K. Shoffner, Santiago Schnell
bioRxiv 034900; doi: https://doi.org/10.1101/034900
Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
Citation Tools
Estimation of the lag time in a subsequent monomer addition model for fibril elongation
Suzanne K. Shoffner, Santiago Schnell
bioRxiv 034900; doi: https://doi.org/10.1101/034900

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Biochemistry
Subject Areas
All Articles
  • Animal Behavior and Cognition (2410)
  • Biochemistry (4765)
  • Bioengineering (3310)
  • Bioinformatics (14607)
  • Biophysics (6600)
  • Cancer Biology (5144)
  • Cell Biology (7389)
  • Clinical Trials (138)
  • Developmental Biology (4330)
  • Ecology (6841)
  • Epidemiology (2057)
  • Evolutionary Biology (9860)
  • Genetics (7322)
  • Genomics (9483)
  • Immunology (4517)
  • Microbiology (12615)
  • Molecular Biology (4909)
  • Neuroscience (28173)
  • Paleontology (198)
  • Pathology (800)
  • Pharmacology and Toxicology (1375)
  • Physiology (2005)
  • Plant Biology (4461)
  • Scientific Communication and Education (973)
  • Synthetic Biology (1295)
  • Systems Biology (3898)
  • Zoology (719)