scholarly journals Slow Dissolution Kinetics of Model Peptide Fibrils

2020 ◽  
Vol 21 (20) ◽  
pp. 7671
Author(s):  
Mona Koder Hamid ◽  
Axel Rüter ◽  
Stefan Kuczera ◽  
Ulf Olsson
Keyword(s):  
Hydrogen Bonds ◽  
Self Assembly ◽  
Amyloid Fibrils ◽  
Dissolution Kinetics ◽  
Titration Calorimetry ◽  
Model Peptide ◽  
Rate Limiting Step ◽  
Low Concentrations ◽  
Peptide Fibrils ◽  
Kinetics Of

Understanding the kinetics of peptide self-assembly is important because of the involvement of peptide amyloid fibrils in several neurodegenerative diseases. In this paper, we have studied the dissolution kinetics of self-assembled model peptide fibrils after a dilution quench. Due to the low concentrations involved, the experimental method of choice was isothermal titration calorimetry (ITC). We show that the dissolution is a strikingly slow and reaction-limited process, that can be timescale separated from other rapid processes associated with dilution in the ITC experiment. We argue that the rate-limiting step of dissolution involves the breaking up of inter-peptide β–sheet hydrogen bonds, replacing them with peptide–water hydrogen bonds. Complementary pH experiments revealed that the self-assembly involves partial deprotonation of the peptide molecules.

scholarly journals Dissecting the self-assembly kinetics of multimeric pore-forming toxins

2016 ◽  
Vol 13 (114) ◽  
pp. 20150762 ◽  
Author(s):  
A. A. Lee ◽  
M. J. Senior ◽  
M. I. Wallace ◽  
T. E. Woolley ◽  
I. M. Griffiths
Keyword(s):  
Single Molecule ◽  
Self Assembly ◽  
Quantitative Agreement ◽  
Time Resolved ◽  
Biologically Relevant ◽  
Low Concentrations ◽  
Assembly Kinetics ◽  
Quantitative Understanding ◽  
Mechanism And Kinetics ◽  
Kinetics Of

Pore-forming toxins are ubiquitous cytotoxins that are exploited by both bacteria and the immune response of eukaryotes. These toxins kill cells by assembling large multimeric pores on the cell membrane. However, a quantitative understanding of the mechanism and kinetics of this self-assembly process is lacking. We propose an analytically solvable kinetic model for stepwise, reversible oligomerization. In biologically relevant limits, we obtain simple algebraic expressions for the rate of pore formation, as well as for the concentration of pores as a function of time. Quantitative agreement is obtained between our model and time-resolved kinetic experiments of Bacillus thuringiensis Cry1Ac (tetrameric pore), aerolysin, Staphylococcus aureus α -haemolysin (heptameric pores) and Escherichia coli cytolysin A (dodecameric pore). Furthermore, our model explains how rapid self-assembly can take place with low concentrations of oligomeric intermediates, as observed in recent single-molecule fluorescence experiments of α-haemolysin self-assembly. We propose that suppressing the concentration of oligomeric intermediates may be the key to reliable, error-free, self-assembly of pores.

scholarly journals Confined self-assembly of cellulose nanocrystals in a shrinking droplet

Soft Matter ◽  
2015 ◽  
Vol 11 (26) ◽  
pp. 5374-5380 ◽  
Author(s):  
Fernando Jativa ◽  
Christina Schütz ◽  
Lennart Bergström ◽  
Xuehua Zhang ◽  
Bernd Wicklein
Keyword(s):  
Cellulose Nanocrystals ◽  
Self Assembly ◽  
Liquid Crystalline ◽  
Dissolution Kinetics ◽  
Crystalline Phases ◽  
Liquid Crystalline Phases ◽  
Kinetics Of

Self-assembly of cellulose nanocrystals in a shrinking droplet was studied. The evolution of liquid crystalline phases and the morphology of the resultant microbeads can be controlled by the dissolution kinetics of the droplet.

Quantitative approaches for characterising fibrillar protein nanostructures

2010 ◽  
Vol 1274 ◽  
Author(s):  
Tuomas P. J. Knowles ◽  
Duncan A. White ◽  
Christopher M. Dobson ◽  
Mark E. Welland
Keyword(s):  
Self Assembly ◽  
Amyloid Fibrils ◽  
Protective Coatings ◽  
Functional Materials ◽  
Protein Deposition ◽  
Disease States ◽  
Parkinson’S Diseases ◽  
Protein Molecules ◽  
Kinetics Of ◽  
Mechanical Fragmentation

AbstractPolypeptide sequences have an inherent tendency to self-assemble into filamentous nanostructures commonly known as amyloid fibrils. Such self-assembly is used in nature to generate a variety of functional materials ranging from protective coatings in bacteria to catalytic scaffolds in mammals. The aberrant self-assembly of misfolded peptides and proteins is also, however, implicated in a range of disease states including neurodegenerative conditions such as Alzheimer's and Parkinson's diseases. It is increasingly evident that the intrinsic material properties of these structures are crucial for understanding the thermodynamics and kinetics of the pathological deposition of proteins, particularly as the mechanical fragmentation of aggregates enhances the rate of protein deposition by exposing new fibril ends which can promote further growth. We discuss here recent advances in physical techniques that are able to characterise the hierarchical self-assembly of misfolded protein molecules and define their properties.

scholarly journals Nucleation-dependent aggregation kinetics of Yeast Sup35 fragment GNNQQNY

2020 ◽  
Author(s):  
Gunasekhar Burra ◽  
Mahmoud B. Maina ◽  
Louise C. Serpell ◽  
Ashwani K. Thakur
Keyword(s):  
Self Assembly ◽  
Amyloid Fibrils ◽  
Peptide Sequence ◽  
Aggregation Kinetics ◽  
Assembly Mechanism ◽  
Structural Identity ◽  
Different Temperatures ◽  
Dynamics Simulations ◽  
Amyloid Assembly ◽  
Kinetics Of

AbstractAn N-terminal hepta-peptide sequence of yeast prion protein Sup35 with the sequence GNNQQNY serves as an ideal model for structural understanding of amyloid assembly and kinetics. In this study, we used a reproducible solubilisation protocol that allows the generation of homogenous monomeric solution of GNNQQNY to understand the molecular details of its self-assembly mechanism. The aggregation kinetics data show that the GNNQQNY sequences follow nucleation-dependent aggregation kinetics with a critical nucleus of size ~7 monomers and that the size and efficiency of nucleation was found to be inversely related to the reaction temperature. The generated nucleus reduces the thermodynamic energy barrier by acting as a template for further self-assembly and results in highly ordered amyloid fibrils. The fibers grown at different temperatures showed similar Thioflavin T positivity, Congo red binding and β-sheet rich structures displaying a characteristic cross-β diffraction pattern. These aggregates also share morphological and structural identity with those reported earlier. The mature GNNQQNY fibers exerted no significant oxidative stress or cytotoxicity upon incubating with differentiated SHSY5Y cells. To our knowledge, this is the first study to experimentally validate previous predictions based on theoretical and molecular dynamics simulations. These findings will provide the basis for understanding the kinetics and thermodynamics of amyloid nucleation and elongation of amyloidogenic systems associated with many systemic and neurodegenerative diseases.

scholarly journals A molecular model of the surface-assisted protein aggregation process

2018 ◽  
Author(s):  
Y.G. Pan ◽  
S. Banerjee ◽  
K. Zagorski ◽  
L.S. Shlyakhtenko ◽  
A.B. Kolomeisky ◽  
...  
Keyword(s):  
Self Assembly ◽  
Molecular Mechanisms ◽  
Molecular Model ◽  
Critical Role ◽  
Experimental Studies ◽  
Cytosine Deaminase ◽  
Aggregation Process ◽  
Amyloidogenic Proteins ◽  
Low Concentrations ◽  
Kinetics Of

AbstractThe importance of cell surfaces in the self-assembly of proteins is widely accepted. One biologically significant event is the assembly of amyloidogenic proteins into aggregates, which leads to neurodegenerative disorders like Alzheimer’s and Parkinson’s. The interaction of amyloidogenic proteins with cellular membranes appears to dramatically facilitate the aggregation process. Recent findings indicate that, in the presence of surfaces, aggregation occurs at physiologically low concentrations, suggesting interaction with surfaces plays a critical role in the disease-prone aggregation process. However, the molecular mechanisms behind on-surface aggregation remain unclear. Here we provide a theoretical model that offers a molecular explanation. According to this model, monomers transiently immobilized to surfaces increase the local monomer protein concentration and thus work as nuclei to dramatically accelerate the entire aggregation process. This theory was verified by experimental studies, using mica surfaces, to examine the aggregation kinetics of amyloidogenic-synuclein protein (α-Syn) and non-amyloidogenic cytosine deaminase APOBEC3G (A3G).

Kinetics of Various 99mTc-Sn-Pyrophosphate Compounds in the Rat

1977 ◽  
Vol 16 (04) ◽  
pp. 157-162 ◽  
Author(s):  
C. Schümichen ◽  
B. Mackenbrock ◽  
G. Hoffmann
Keyword(s):  
Normal Saline ◽  
Half Life ◽  
Compound A ◽  
Short Half Life ◽  
Low Concentrations ◽  
The Stability ◽  
Kinetics Of ◽  
In Vitro Stability

SummaryThe bone-seeking 99mTc-Sn-pyrophosphate compound (compound A) was diluted both in vitro and in vivo and proved to be unstable both in vitro and in vivo. However, stability was much better in vivo than in vitro and thus the in vitro stability of compound A after dilution in various mediums could be followed up by a consecutive evaluation of the in vivo distribution in the rat. After dilution in neutral normal saline compound A is metastable and after a short half-life it is transformed into the other 99mTc-Sn-pyrophosphate compound A is metastable and after a short half-life in bone but in the kidneys. After dilution in normal saline of low pH and in buffering solutions the stability of compound A is increased. In human plasma compound A is relatively stable but not in plasma water. When compound B is formed in a buffering solution, uptake in the kidneys and excretion in urine is lowered and blood concentration increased.It is assumed that the association of protons to compound A will increase its stability at low concentrations while that to compound B will lead to a strong protein bond in plasma. It is concluded that compound A will not be stable in vivo because of a lack of stability in the extravascular space, and that the protein bond in plasma will be a measure of its in vivo stability.

In situ Time-Resolved Small-Angle X-ray Scattering Reveals the Formation Kinetics of Polyelectrolyte Complex Micelles

2019 ◽  
Author(s):  
Hao Wu ◽  
Jeffrey Ting ◽  
Siqi Meng ◽  
Matthew Tirrell
Keyword(s):  
Small Angle ◽  
Self Assembly ◽  
Electrostatic Interactions ◽  
Polyelectrolyte Complex ◽  
Time Resolved ◽  
X Ray ◽  
X Ray Scattering ◽  
Kinetics Of ◽  
Ray Scattering

We have directly observed the <i>in situ</i> self-assembly kinetics of polyelectrolyte complex (PEC) micelles by synchrotron time-resolved small-angle X-ray scattering, equipped with a stopped-flow device that provides millisecond temporal resolution. This work has elucidated one general kinetic pathway for the process of PEC micelle formation, which provides useful physical insights for increasing our fundamental understanding of complexation and self-assembly dynamics driven by electrostatic interactions that occur on ultrafast timescales.

Submerged upflow biotower operation and computer simulation

1994 ◽  
Vol 30 (11) ◽  
pp. 143-146
Author(s):  
Ronald D. Neufeld ◽  
Christopher A. Badali ◽  
Dennis Powers ◽  
Christopher Carson
Keyword(s):  
Computer Simulation ◽  
Benzoic Acid ◽  
Computer Model ◽  
Rate Constants ◽  
Batch Mode ◽  
Operational Conditions ◽  
First Order ◽  
Low Concentrations ◽  
Biological Transformation ◽  
Kinetics Of

A two step operation is proposed for the biodegradation of low concentrations (&lt; 10 mg/L) of BETX substances in an up flow submerged biotower configuration. Step 1 involves growth of a lush biofilm using benzoic acid in a batch mode. Step 2 involves a longer term biological transformation of BETX. Kinetics of biotransformations are modeled using first order assumptions, with rate constants being a function of benzoic acid dosages used in Step 1. A calibrated computer model is developed and presented to predict the degree of transformation and biomass level throughout the tower under a variety of inlet and design operational conditions.

Kinetics of cyclization of S-ethoxycarbonylmethylisothiouronium chloride to 2-imino-4-thiazolidone

1979 ◽  
Vol 44 (3) ◽  
pp. 912-917 ◽  
Author(s):  
Vladimír Macháček ◽  
Said A. El-bahai ◽  
Vojeslav Štěrba
Keyword(s):  
Hydrochloric Acid ◽  
Dilute Hydrochloric Acid ◽  
Base Catalysis ◽  
General Base ◽  
Rate Limiting Step ◽  
Limiting Step ◽  
Kinetics Of Formation ◽  
Acid Catalyzed ◽  
Rate Limiting ◽  
Kinetics Of

Kinetics of formation of 2-imino-4-thiazolidone from S-ethoxycarbonylmethylisothiouronium chloride has been studied in aqueous buffers and dilute hydrochloric acid. The reaction is subject to general base catalysis, the β value being 0.65. Its rate limiting step consists in acid-catalyzed splitting off of ethoxide ion from dipolar tetrahedral intermediate. At pH < 2 formation of this intermediate becomes rate-limiting; rate constant of its formation is 2 . 104 s-1.

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