Advanced

Amyloid Nucleation in Presence of Crowders

Wessén, Jonas LU (2014) FYTM02 20141
Department of Astronomy and Theoretical Physics
Computational Biology and Biological Physics
Abstract
During the last few years, crowding effects on the physics of proteins has become an increasingly popular topic of research. This is is because most biological processes involving proteins naturally take place in a crowded environment, e.g. in the cellular environment where macromolecules may occupy 30% of the volume. One such biological process would be the formation of amyloid aggregates, which are cross-beta-sheet rich protein structures that have been associated with e.g. Alzheimer's disease. In this work, we investigate the crowding effects on the formation of amyloid fibrils by adding neutral crowding particles (i.e. no explicit interaction except excluded volume effects) to a lattice model of a solution of short peptides. The... (More)
During the last few years, crowding effects on the physics of proteins has become an increasingly popular topic of research. This is is because most biological processes involving proteins naturally take place in a crowded environment, e.g. in the cellular environment where macromolecules may occupy 30% of the volume. One such biological process would be the formation of amyloid aggregates, which are cross-beta-sheet rich protein structures that have been associated with e.g. Alzheimer's disease. In this work, we investigate the crowding effects on the formation of amyloid fibrils by adding neutral crowding particles (i.e. no explicit interaction except excluded volume effects) to a lattice model of a solution of short peptides. The peptides in the model interact via nearest neighbour interactions which under certain conditions cause formation of amyloid-like protein aggregates. We hypothesise that the dominant effect of such crowding can be derived from the effective increase in the peptide density, which depends on the total volume occupied by the crowding particles (`crowders'), and not on the total surface area of the crowders, as have recently been discussed in the literature. Any dominant surface effects, such as the recently observed dual effect on the aggregation kinetics of amyloid beta fibrils, is likely due to an explicit interaction between the crowding particles and the peptides.

In addition, we develop an analytical approach that permits us to study the thermodynamics of the model without crowders. In this approach, we treat the collection of each type (i.e. of given length and width) of aggregates in the system as a collection of non-interacting objects in grand-canonical ensembles, with the over-all constraint of peptide number conservation. This method is used to study systems much larger than those we can simulate using Monte Carlo methods, and to compute an approximate phase diagram for the model. (Less)
Please use this url to cite or link to this publication:
author
Wessén, Jonas LU
supervisor
organization
course
FYTM02 20141
year
type
H1 - Master's Degree (One Year)
subject
keywords
nucleation, molecular self-assembly, protein physics, statistical mechanics, thermodynamics, fibrilation kinetics, Monte Carlo, Huntington's, Parkinson's, Alzheimer's, molecular crowding, amyloid fibrils, amyloid, protein aggregation
language
English
id
4519439
date added to LUP
2014-06-27 14:30:39
date last changed
2014-06-27 14:39:32
@misc{4519439,
  abstract     = {During the last few years, crowding effects on the physics of proteins has become an increasingly popular topic of research. This is is because most biological processes involving proteins naturally take place in a crowded environment, e.g. in the cellular environment where macromolecules may occupy 30% of the volume. One such biological process would be the formation of amyloid aggregates, which are cross-beta-sheet rich protein structures that have been associated with e.g. Alzheimer's disease. In this work, we investigate the crowding effects on the formation of amyloid fibrils by adding neutral crowding particles (i.e. no explicit interaction except excluded volume effects) to a lattice model of a solution of short peptides. The peptides in the model interact via nearest neighbour interactions which under certain conditions cause formation of amyloid-like protein aggregates. We hypothesise that the dominant effect of such crowding can be derived from the effective increase in the peptide density, which depends on the total volume occupied by the crowding particles (`crowders'), and not on the total surface area of the crowders, as have recently been discussed in the literature. Any dominant surface effects, such as the recently observed dual effect on the aggregation kinetics of amyloid beta fibrils, is likely due to an explicit interaction between the crowding particles and the peptides. 

In addition, we develop an analytical approach that permits us to study the thermodynamics of the model without crowders. In this approach, we treat the collection of each type (i.e. of given length and width) of aggregates in the system as a collection of non-interacting objects in grand-canonical ensembles, with the over-all constraint of peptide number conservation. This method is used to study systems much larger than those we can simulate using Monte Carlo methods, and to compute an approximate phase diagram for the model.},
  author       = {Wessén, Jonas},
  keyword      = {nucleation,molecular self-assembly,protein physics,statistical mechanics,thermodynamics,fibrilation kinetics,Monte Carlo,Huntington's,Parkinson's,Alzheimer's,molecular crowding,amyloid fibrils,amyloid,protein aggregation},
  language     = {eng},
  note         = {Student Paper},
  title        = {Amyloid Nucleation in Presence of Crowders},
  year         = {2014},
}