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

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.

Nanoscale Surface Topography Modulates hIAPP Aggregation Pathways at Solid–Liquid Interfaces

“…On the contrary, it appears that the presence of the surface leads to a delay in aggregation. This is in agreement with the Monte Carlo simulations by Co and Li, which revealed that the presence of a weakly adsorbing surface may indeed slow down peptide aggregation [ 24 ]. For this type of surface, the authors also observed that increasing the surface roughness led to a further delay in aggregation.…”

“…This was explained by the rougher surfaces hindering the lateral diffusion of adsorbed peptide monomers along the surface, which prevented them from reaching and attaching to the ends of growing amyloid fibrils. This was recently verified by Co and Li in Monte Carlo simulations [ 24 ]. In this work, we investigate the effect of nanoscale surface topography on the aggregation of human islet amyloid polypeptide (hIAPP) at hydrophilic silicon oxide surfaces.…”

“…Even though the effects of different nanoscale surface topographies on the adsorption of various proteins have been investigated in numerous studies [ 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 ], the underlying mechanisms are still not yet fully understood. This particularly concerns the question of how surface topography may affect also protein–protein interactions and protein aggregation during adsorption [ 14 , 21 , 22 , 23 , 24 ].…”

“…While several studies have investigated the influence of surface chemistry and wettability on amyloid aggregation [ 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 ], there are only a few publications so far that have addressed the effect of surface topography [ 23 , 24 , 62 ]. Shezad et al investigated the aggregation of the Alzheimer’s-associated peptide Aβ(1–42) at hydrophobic polystyrene (PS) surfaces with random rough surface topographies [ 23 ].…”

Changes in the Secondary Structure and Assembly of Proteins on Fluoride Ceramic (CeF3) Nanoparticle Surfaces

“… 11 The rate of peptide aggregation on the solid–liquid interface is determined by the affinity (binding force) between the peptide and the solid material and the shape (roughness) of the solid surface. 12 While a high affinity between peptides and solid surfaces enhances their adsorption and inhibits the self-assembly (aggregation) of peptides, solid materials with middle affinities and a rough surface (with a nanoscale morphology) accelerate the aggregation of peptides. In contrast, in a study in which all-atom MD simulations of the conformation of Aβ 16–22 peptides were performed, hydrophobic interactions were found to prevent the formation of β-sheet structures in the presence of gold nanoparticles (NPs).…”