Nanoparticle mobility over a surface as a probe for weak transient disordered peptide-peptide interactions

TL;DR

This paper introduces a novel single particle tracking method using peptide-coated gold nanoparticles to quantitatively analyze weak, transient peptide-peptide interactions, including effects of mutations and buffer conditions, with high sensitivity.

Contribution

The study presents a new, efficient technique for probing weak peptide interactions at the single-molecule level, applicable to disordered proteins and biomolecules.

Findings

Sensitive detection of single amino acid mutation effects

Quantitative analysis of buffer salinity impact

Potential for high-throughput evaluation of weak interactions

Abstract

Weak interactions form the core basis of a vast number of biological processes, in particular, those involving intrinsically disordered proteins. Here, we establish a new technique capable of probing these weak interactions between synthetic unfolded polypeptides using a convenient yet efficient, quantitative method based on single particle tracking of peptide-coated gold nanoparticles over peptide-coated surfaces. We demonstrate that our technique is sensitive enough to observe the influence of a single amino acid mutation on the transient peptide-peptide interactions. Furthermore, the effects of buffer salinity, expected to alter weak electrostatic interactions, are also readily detected and examined in detail. The method presented here has the potential to evaluate in a high throughput manner, weak interactions for a wide range of disordered proteins, polypeptides, and other biomolecules.