Direct Observation of Aβ Amyloid Fibril Growth and Inhibition

Ban, Takashi; Hoshino, Minoru; Takahashi, Satoshi; Hamada, Daizo; Hara, Kazuhiro; Naiki, Hironobu; Goto, Yuji

doi:10.1016/j.jmb.2004.09.078

Cited by 226 publications

(319 citation statements)

References 47 publications

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“…A rough estimate of t diff can be obtained from the reaction rate for particles approaching an absorbing sphere, 4π acD p , where a is the radius of the absorbing surface, c is the concentration far from the surface, and D p is the diffusion constant of the particles. To describe the growth rates of fibrils bound to a surface 26,27 this must be reduced by half to account for the 2π solid angle restriction…”

Section: Model a Fibril Order Is Determined By A Competition Betmentioning

confidence: 99%

“…The key timescales in the growth process can be summarized k −1 grow t wait , t diff k −1 + , with an impressive 8 to 9 orders of magnitude separating the macroscopic growth rate from the microscopic timescale of H-bond formation. 26,27 In addition, Eq. (11) shows that the timescale governing growth in the reaction limited regime, t wait t diff , is not the annealing of newly bound molecules, but the clearance of off-pathway intermediates.…”

Section: Ordered Fibril Growth Requires Incoming Molecules To Sampmentioning

confidence: 99%

“…27 To compare this value to the theory I approximate t diff (Eq. (3)) using the Stokes-Einstein relation for the diffusion constant…”

Section: A Growth Rates Are Limited By the Low Probability Of In-regmentioning

confidence: 99%

See 2 more Smart Citations

Kinetic theory of amyloid fibril templating

Schmit

2013

The Journal of Chemical Physics

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The growth of amyloid fibrils requires a disordered or partially unfolded protein to bind to the fibril and adapt the same conformation and alignment established by the fibril template. Since the H-bonds stabilizing the fibril are interchangeable, it is inevitable that H-bonds form between incorrect pairs of amino acids which are either incorporated into the fibril as defects or must be broken before the correct alignment can be found. This process is modeled by mapping the formation and breakage of H-bonds to a one-dimensional random walk. The resulting microscopic model of fibril growth is governed by two timescales: the diffusion time of the monomeric proteins, and the time required for incorrectly bound proteins to unbind from the fibril. The theory predicts that the Arrhenius behavior observed in experiments is due to off-pathway states rather than an on-pathway transition state. The predicted growth rates are in qualitative agreement with experiments on insulin fibril growth rates as a function of protein concentration, denaturant concentration, and temperature. These results suggest a templating mechanism where steric clashes due to a single mis-aligned molecule prevent the binding of additional molecules.

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Section: Model a Fibril Order Is Determined By A Competition Betmentioning

confidence: 99%

Section: Ordered Fibril Growth Requires Incoming Molecules To Sampmentioning

confidence: 99%

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Kinetic theory of amyloid fibril templating

Schmit

2013

The Journal of Chemical Physics

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“…More recently, other methods have been developed that enable the growth of individual fibrils to be directly monitored with atomic force microscopy (AFM) (15)(16)(17)(18)(19)(20), total internal reflection fluorescence microscopy (21), or experiments that detect the growth of an ensemble of fibrils by surface plasmon resonance (22) or dynamic light scattering (13). In addition, methods have emerged that concentrate on monitoring, by mass spectrometry (23) or high-performance liquid chromatography (24), the changes in the concentrations of the precursor protein as a measure of its incorporation into growing fibrils.…”

mentioning

confidence: 99%

Kinetics and thermodynamics of amyloid formation from direct measurements of fluctuations in fibril mass

Knowles

Shu

Devlin

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

190

242

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Aggregation of proteins and peptides is a widespread and muchstudied problem, with serious implications in contexts ranging from biotechnology to human disease. An understanding of the proliferation of such aggregates under specific conditions requires a quantitative knowledge of the kinetics and thermodynamics of their formation; measurements that to date have remained elusive. Here, we show that precise determination of the growth rates of ordered protein aggregates such as amyloid fibrils can be achieved through real-time monitoring, using a quartz crystal oscillator, of the changes in the numbers of molecules in the fibrils from variations in their masses. We show further that this approach allows the effect of other molecular species on fibril growth to be characterized quantitatively. This method is widely applicable, and we illustrate its power by exploring the free-energy landscape associated with the conversion of the protein insulin to its amyloid form and elucidate the role of a chemical chaperone and a small heat shock protein in inhibiting the aggregation reaction.protein aggregation ͉ quartz crystal microbalance ͉ biosensors

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“…Recently, the growth of individual amyloid fibrils was observed by using atomic force microscopy (AFM) (6, 7) and fluorescence microscopic methods (8,9). In some experiments, a stop-and-run phenomenon was observed, during which the fibril growth was temporarily halted (9,10), whereas others pointed to a constant growth rate (8,9). The lack of either high spatial or high temporal resolution, however, hid the greater detail of the assembly process.…”

mentioning

confidence: 99%

Stepwise dynamics of epitaxially growing single amyloid fibrils

Kellermayer

Karsai

Benke

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

104

121

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The assembly mechanisms of amyloid fibrils, tissue deposits in a variety of degenerative diseases, is poorly understood. With a simply modified application of the atomic force microscope, we monitored the growth, on mica surface, of individual fibrils of the amyloid ␤25-35 peptide with near-subunit spatial and subsecond temporal resolution. Fibril assembly was polarized and discontinuous. Bursts of rapid (up to 300-nm ؊1 ) growth phases that extended the fibril by Ϸ7 nm or its integer multiples were interrupted with pauses. Stepwise dynamics were also observed for amyloid ␤1-42 fibrils growing on graphite, suggesting that the discontinuous assembly mechanisms may be a general feature of epitaxial amyloid growth. Amyloid assembly may thus involve fluctuation between a fast-growing and a blocked state in which the fibril is kinetically trapped because of intrinsic structural features. The used scanning-force kymography method may be adapted to analyze the assembly dynamics of a wide range of linear biopolymers.atomic force microscopy ͉ beta-amyloid ͉ growth dynamics ͉ self-assembly

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Direct Observation of Aβ Amyloid Fibril Growth and Inhibition

Cited by 226 publications

References 47 publications

Kinetic theory of amyloid fibril templating

Kinetic theory of amyloid fibril templating

Kinetics and thermodynamics of amyloid formation from direct measurements of fluctuations in fibril mass

Stepwise dynamics of epitaxially growing single amyloid fibrils

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