Effect of Surface Roughness on Aggregation of Polypeptide Chains: A Monte Carlo Study.

Nguyen Co,Mai Li

doi:10.3390/biom11040596

Abstract

The self-assembly of amyloidogenic peptides and proteins into fibrillar structures has been intensively studied for several decades, because it seems to be associated with a number of neurodegenerative diseases, such as Alzheimer’s and Parkinson’s disease. Therefore, understanding the molecular mechanisms of this phenomenon is important for identifying an effective therapy for the corresponding diseases. Protein aggregation in living organisms very often takes place on surfaces like membranes and the impact of a surface on this process depends not only on the surface chemistry but also on its topology. Our goal was to develop a simple lattice model for studying the role of surface roughness in the aggregation kinetics of polypeptide chains and the morphology of aggregates. We showed that, consistent with the experiment, an increase in roughness slows down the fibril formation, and this process becomes inhibited at a very highly level of roughness. We predicted a subtle catalytic effect that a slightly rough surface promotes the self-assembly of polypeptide chains but does not delay it. This effect occurs when the interaction between the surface and polypeptide chains is moderate and can be explained by taking into account the competition between energy and entropy factors.

Highlights

The self-assembly of proteins into aggregates of various morphologies is probably one of the main causes of chronic neurodegenerative diseases such as Alzheimer’s, Parkinson’s and Huntington’s disease [1,2,3]
Protein aggregation can occur in solution as well as in complex environments, including various surrounding objects such as cell membranes, DNA, sugars, other biological compounds and industrial artificial surfaces which require the careful study of the effect of different surfaces on the process [4,5,6,7,8]
We develop simple lattice models in which rough surfaces were created by randomly distributed balls on smooth planes and performed Monte Carlo simulations to explain the experimentally observed phenomena

Summary

Introduction

The self-assembly of proteins into aggregates of various morphologies is probably one of the main causes of chronic neurodegenerative diseases such as Alzheimer’s, Parkinson’s and Huntington’s disease [1,2,3]. Understanding the mechanisms of protein aggregation plays an important role in discovering effective therapies to treat these diseases. Protein aggregation can occur in solution as well as in complex environments, including various surrounding objects such as cell membranes, DNA, sugars, other biological compounds and industrial artificial surfaces which require the careful study of the effect of different surfaces on the process [4,5,6,7,8]. The impact of foreign surfaces on the protein aggregation process displays complicated behaviors which depend on the type of surfaces, proteins and experiment conditions [9,10,11,12]. Lipid membranes were reported to play the role of a template to accelerate the aggregation of different amyloidogenic peptides [13,14,15,16]. Mica and glass facilitated the fibril formation of the fragment Aβ18-22 [17]

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Results