2016
DOI: 10.1039/c5cp07845h
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Estimation of the lag time in a subsequent monomer addition model for fibril elongation

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 with a 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 cann… Show more

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Cited by 38 publications
(30 citation statements)
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“…2d ). But interestingly, the time lag observed in absorbance ( t lag (Abs 500 nm ) = 203 s) was lesser than the CD time lag ( t lag (CD 500 nm ) = 280 s) 46 (Supplementary Fig. 11 and Supplementary Table 1 ).…”
Section: Resultsmentioning
confidence: 92%
“…2d ). But interestingly, the time lag observed in absorbance ( t lag (Abs 500 nm ) = 203 s) was lesser than the CD time lag ( t lag (CD 500 nm ) = 280 s) 46 (Supplementary Fig. 11 and Supplementary Table 1 ).…”
Section: Resultsmentioning
confidence: 92%
“…Amyloid fibril formation is most commonly monitored by measuring the fluorescence of thioflavin T (ThT), a small molecular dye that becomes highly emissive when intercalated into the β-sheets of amyloidogenic oligomers and fibrils (LeVine, 1999). ThT kinetics of amyloid fibril formation can be divided into three distinct phases (Fig 1A): the nucleation (i.e., lag) phase, in which soluble monomers undergo structural changes and nucleate; the elongation (i.e., growth) phase, during which ThT-positive oligomers and protofibrils form; and the equilibration (i.e., plateau) phase, in which mature fibrils undergo cycles of shedding and seeding (Shoffner & Schnell, 2016).…”
Section: Resultsmentioning
confidence: 99%
“…Longer lag times could reect a partial suppression of primary nucleation. 43,44 This step is dependent on at least two factors: (1) the distribution of conformations, i.e. folded or (partially) unfolded vs. nucleation-prone, and (2) the diffusion of these molecules in solution determining the rate of interactions between molecules.…”
Section: Resultsmentioning
confidence: 99%