Empirical Optimization of Peptide Sequence and Nanoparticle Colloidal Stability: The Impact of Surface Ligands and Implications for Colorimetric Sensing

Abstract

Surface ligands play a critical role in controlling and defining the properties of colloidal nanocrystals. These aspects have been exploited to design nanoparticle aggregation-based colorimetric sensors. Here, we coated 13-nm gold nanoparticles (AuNPs) with a large library of ligands (e.g., from labile monodentate monomers to multicoordinating macromolecules) and evaluated their aggregation propensity in the presence of three peptides containing charged, thiolate, or aromatic amino acids. Our results show that AuNPs coated with the polyphenols and sulfonated phosphine ligands were good choices for electrostaticbased aggregation. AuNPs capped with citrate and labile-binding polymers worked well for dithiol-bridging and π−π stacking-induced aggregation. In the example of electrostatic-based assays, we stress that good sensing performance requires aggregating peptides of low charge valence paired with charged NPs with weak stability and vice versa. We then present a modular peptide containing versatile aggregating residues to agglomerate a variety of ligated AuNPs for colorimetric detection of the coronavirus main protease. Enzymatic cleavage liberates the peptide segment, which in turn triggers NP agglomeration and thus rapid color changes in <10 min. The protease detection limit is 2.5 nM.

An approach to zwitterionic peptide design for colorimetric detection of the Southampton norovirus SV3CP protease

“…These results are largely consistent with our past studies of this specific ligand exchange. 7,9 Furthermore, a Fourier transform infrared (FTIR) spectroscopy of the particles before and after the ligand exchange shows the removal of most of the native citrate and binding of the BSPP ligand onto the nanoparticle surface (Fig. 1c and d), as noted by symmetrical and asymmetrical stretching of the S–O bond from the BSPP ligand, indicating a successful ligand exchange.…”

“…18,19 Functionalization of AuNPs with the BSPP ligand gave the nanoparticles considerable colloidal stability relative to the native citrate particles. 7 This stability is due to the strong negative charges found in the sulfonate groups of BSPP, effective gold-phosphorous gold coordination, steric hindrance from bulky aromatic rings, and strong electrostatic double layer repulsions. 20 As a result, the BSPP-capped nanoparticles can remain colloidally stable in various media, making them suitable for use in buffers and higher salt concentrations.…”

“…6 Additionally, surface modifications of AuNPs can provide diverse functionalization options that allow for robust interfacing of the particles through electrostatic, dithiol bridging, or amphiphilic interactions to promote aggregation. 7–10…”

A machine learning-based colorimetric sensor array for high-precision pathogen identification in household refrigerators

“…In addition, the standard responses of the CSA to other signature VOCs of meat and seafood, including primary amines and trimethylamine (dye spots 6–8), H 2 S (dye spot 11), and acetic acid (dye spots 15 and 16), also show distinctive color variation patterns. 21 The above studies demonstrate that the response patterns of CSA to VOCs were different. Therefore, 16 chromogenic dyes and dye combinations are selected in anticipation of obtaining distinguishable responses to VOCs produced by common foodborne pathogens in household refrigerators (Table S4, ESI†).…”

Goldilocks Energy Minimum: Peptide-Based Reversible Aggregation and Biosensing

“…Sensors based on this mechanism often have poor specificity and limited utility with clinical samples for several reasons. First, citrate-stabilized AuNPs are very sensitive to pH, solvent polarity, and ionic strengthall of these can cause undesired aggregation and thus require surface modifications of the particles (e.g., PEGylation, BSPP). − Second, biofluids such as plasma, serum, saliva, sweat, or urine can lead to a protein corona, thus changing the surface charge and preventing electrostatic-based plasmonic coupling . Third, AuNP colloidal stability is notoriously dependent on ionic strengthphysiological salt concentrations can lead to charge screening of the electrostatic repulsions thus allowing attractive VdW to predominate.…”