A modified Stokes-Einstein equation for Aβ aggregation

Srisairam Achuthan, Bong J. Chung, Preetam Ghosh, Vijayaraghavan Rangachari, Ashwin Vaidya

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Background: In all amyloid diseases, protein aggregates have been implicated fully or partly, in the etiology of the disease. Due to their significance in human pathologies, there have been unprecedented efforts towards physiochemical understanding of aggregation and amyloid formation over the last two decades. An important relation from which hydrodynamic radii of the aggregate is routinely measured is the classic Stokes-Einstein equation. Here, we report a modification in the classical Stokes-Einstein equation using a mixture theory approach, in order to accommodate the changes in viscosity of the solvent due to the changes in solute size and shape, to implement a more realistic model for Aβ aggregation involved in Alzheimer's disease. Specifically, we have focused on validating this model in protofibrill lateral association reactions along the aggregation pathway, which has been experimentally well characterized.Results: The modified Stokes-Einstein equation incorporates an effective viscosity for the mixture consisting of the macromolecules and solvent where the lateral association reaction occurs. This effective viscosity is modeled as a function of the volume fractions of the different species of molecules. The novelty of our model is that in addition to the volume fractions, it incorporates previously published reports on the dimensions of the protofibrils and their aggregates to formulate a more appropriate shape rather than mere spheres. The net result is that the diffusion coefficient which is inversely proportional to the viscosity of the system is now dependent on the concentration of the different molecules as well as their proper shapes. Comparison with experiments for variations in diffusion coefficients over time reveals very similar trends.Conclusions: We argue that the standard Stokes-Einstein's equation is insufficient to understand the temporal variations in diffusion when trying to understand the aggregation behavior of Aβ42 proteins. Our modifications also involve inclusion of improved shape factors of molecules and more appropriate viscosities. The modification we are reporting is not only useful in Aβ aggregation but also will be important for accurate measurements in all protein aggregation systems.

Original languageEnglish
Article numberS13
JournalBMC Bioinformatics
Volume12
Issue numberSUPPL. 10
DOIs
StatePublished - 18 Oct 2011

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Stokes Equations
Einstein Equations
Viscosity
Aggregation
Agglomeration
Molecules
Proteins
Protein
Amyloid
Volume Fraction
Diffusion Coefficient
Lateral
Volume fraction
Amyloidogenic Proteins
Association reactions
Mixture Theory
Hydrodynamics
Alzheimer's Disease
Pathology
Macromolecules

Cite this

Achuthan, Srisairam ; Chung, Bong J. ; Ghosh, Preetam ; Rangachari, Vijayaraghavan ; Vaidya, Ashwin. / A modified Stokes-Einstein equation for Aβ aggregation. In: BMC Bioinformatics. 2011 ; Vol. 12, No. SUPPL. 10.
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A modified Stokes-Einstein equation for Aβ aggregation. / Achuthan, Srisairam; Chung, Bong J.; Ghosh, Preetam; Rangachari, Vijayaraghavan; Vaidya, Ashwin.

In: BMC Bioinformatics, Vol. 12, No. SUPPL. 10, S13, 18.10.2011.

Research output: Contribution to journalArticle

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T1 - A modified Stokes-Einstein equation for Aβ aggregation

AU - Achuthan, Srisairam

AU - Chung, Bong J.

AU - Ghosh, Preetam

AU - Rangachari, Vijayaraghavan

AU - Vaidya, Ashwin

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N2 - Background: In all amyloid diseases, protein aggregates have been implicated fully or partly, in the etiology of the disease. Due to their significance in human pathologies, there have been unprecedented efforts towards physiochemical understanding of aggregation and amyloid formation over the last two decades. An important relation from which hydrodynamic radii of the aggregate is routinely measured is the classic Stokes-Einstein equation. Here, we report a modification in the classical Stokes-Einstein equation using a mixture theory approach, in order to accommodate the changes in viscosity of the solvent due to the changes in solute size and shape, to implement a more realistic model for Aβ aggregation involved in Alzheimer's disease. Specifically, we have focused on validating this model in protofibrill lateral association reactions along the aggregation pathway, which has been experimentally well characterized.Results: The modified Stokes-Einstein equation incorporates an effective viscosity for the mixture consisting of the macromolecules and solvent where the lateral association reaction occurs. This effective viscosity is modeled as a function of the volume fractions of the different species of molecules. The novelty of our model is that in addition to the volume fractions, it incorporates previously published reports on the dimensions of the protofibrils and their aggregates to formulate a more appropriate shape rather than mere spheres. The net result is that the diffusion coefficient which is inversely proportional to the viscosity of the system is now dependent on the concentration of the different molecules as well as their proper shapes. Comparison with experiments for variations in diffusion coefficients over time reveals very similar trends.Conclusions: We argue that the standard Stokes-Einstein's equation is insufficient to understand the temporal variations in diffusion when trying to understand the aggregation behavior of Aβ42 proteins. Our modifications also involve inclusion of improved shape factors of molecules and more appropriate viscosities. The modification we are reporting is not only useful in Aβ aggregation but also will be important for accurate measurements in all protein aggregation systems.

AB - Background: In all amyloid diseases, protein aggregates have been implicated fully or partly, in the etiology of the disease. Due to their significance in human pathologies, there have been unprecedented efforts towards physiochemical understanding of aggregation and amyloid formation over the last two decades. An important relation from which hydrodynamic radii of the aggregate is routinely measured is the classic Stokes-Einstein equation. Here, we report a modification in the classical Stokes-Einstein equation using a mixture theory approach, in order to accommodate the changes in viscosity of the solvent due to the changes in solute size and shape, to implement a more realistic model for Aβ aggregation involved in Alzheimer's disease. Specifically, we have focused on validating this model in protofibrill lateral association reactions along the aggregation pathway, which has been experimentally well characterized.Results: The modified Stokes-Einstein equation incorporates an effective viscosity for the mixture consisting of the macromolecules and solvent where the lateral association reaction occurs. This effective viscosity is modeled as a function of the volume fractions of the different species of molecules. The novelty of our model is that in addition to the volume fractions, it incorporates previously published reports on the dimensions of the protofibrils and their aggregates to formulate a more appropriate shape rather than mere spheres. The net result is that the diffusion coefficient which is inversely proportional to the viscosity of the system is now dependent on the concentration of the different molecules as well as their proper shapes. Comparison with experiments for variations in diffusion coefficients over time reveals very similar trends.Conclusions: We argue that the standard Stokes-Einstein's equation is insufficient to understand the temporal variations in diffusion when trying to understand the aggregation behavior of Aβ42 proteins. Our modifications also involve inclusion of improved shape factors of molecules and more appropriate viscosities. The modification we are reporting is not only useful in Aβ aggregation but also will be important for accurate measurements in all protein aggregation systems.

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