Background and Motivation

Assembling nanoparticles in precise structures can lead to unique optical, physical, and electronic properties. However, there are limited tools to precisely control the electrostatic and Van der Waals forces that govern nanoparticle assembly.

Current Efforts

In our work, we have recently shown that small peptides such as arginine and arginine-lysine can assemble precious metal nanoparticles into interesting shapes via diffusion-limited aggregation. We can make this assembly selective for unique chemical biomarkers, such as proteases, in order to detect disease.

Future Work

We have ongoing projects to further understand the structure-function relationship between the peptide identity, and the surface chemistry of the nanoparticle building blocks to design more exogenous structures. We are also working on supermolecular assembly to connect these snowflake-like designs into higher-order aggregates.

Relevant Papers

Retout M, Mantri Y, Jin Z, Zhou J, Noel G, Donovan B, Yim W, Jokerst JV. Peptide-induced fractal assembly of silver nanoparticles for visual detection of disease biomarkers. ACS Nano 2022, 16(4): 6165-6175. [Link]

Retout M, Jin Z, Tsujimoto J, Mantri Y, Borum R, Creyer MC, Yim W, He T, Chang Y, Jokerst JV. Di-arginine additives for dissociation of gold nanoparticle aggregates: A matrix-insensitive approach with applications in protease detection, ACS Applied Materials & Interfaces 2022, 14(46): 52553−52565. [Link]

Chang YC, Jin Z, Li Km Zhou J, Yim W, Yeung J, Cheng Y, Retout M, Creyer M, Fajtova P, He T, Chen X, O'Donoghue AJ, Jokerst JV. Peptide valence-induced breaks in plasmonic coupling. Chemical Science 2023, 10(14): 2659 - 2668. [Link]

Retout M, Amer L, Yim W, Creyer M, Lam B, Trujilio DF, Potempa J, O'Donoghue AF, Jokerst JV. A protease-responsive polymer/peptide conjugate and reversible assembly of silver clusters for the detection of porphyromonas gingivalis enzymatic activity. ACS Nano 2023, 17(17): 17308-17319. [Link]

Project 2. Protease Detection

Background and Motivation

Proteases play pivotal roles to both mammalian cells and pathogens, such as bacteria and viruses. Protease detection currently largely relies on enzyme-linked immunosorbent assay, which suffers from long turnaround times and the need for a lab-based infrastructure. Point-of-care applications have significant potential value in animal and human health as proteases can be diagnostic of numerous diseases, including infections by SARS-class viruses.

Current Efforts

In our work, we have recently developed a portfolio of small molecule and nanoparticle imaging agents to quantify proteases both in in vitro and in vivo scenarios.

Future Work

To continue to explore the value of proteases, our future goals involve integrating additional biomarkers and proteases via substrate profiling. We also desire to include validation of our protease imaging agents within vivo models of human disease.

Relevant Papers

Jin Z, Mantri Y, Retout M, Cheng Y, Zhou J, Jorns A, Fajtova P, Yim W, Moore C, Xu M, Creyer M, Borum R, Zhou J, Wu Z, He T, Penny W, O'Donoghue A, Jokerst JV. A charge-switchable zwitterionic peptide for rapid detection of SARS-CoV-2 main protease. Angewandte Chemie International Edition 2022, 61(9): 1-9. [Link]

Jin Z, Yeung J, Zhou J, Retout M, Yim W, Fajtová P, Goddelin B, Jabin I, Bruylants G, Mattoussi H, O'Donoghue AJ, Jokerst JV. Empirical optimization of peptide sequence and nanoparticle colloidal stability: The impact of surface ligands and implications for colorimetric sensing. ACS Applied Materials and Interfaces 2023, 15(16): 20483-20494. [Link]

Jin Z, Ling, C, Yim W, Chang YC, He T, Li K, Zhou J, Cheng Y, Li Y, Yeung J, Wang R, Fajtová P, Amer L, Mattoussi H, O'Donoghue AJ, Jokerst JV. Endoproteolysis of oligopeptide-based coacervates for enzymatic modeling. ACS Nano 2023, 17(17): 16980-16992. [Link]

Project 3. Cell Imaging Reagents

Background and Motivation

Cell microscopy serves as a workhorse of molecular biology laboratories, consistently relied upon for its valuable insights. As a result, the molecular biology community is constantly in need of new tools to quantify structures on and within cells.

Current Efforts

We have developed agents unique to cell markers, such as TMPRSS2, to assist with this constant demand. We have validated these reagents with flow cytometry and microscopy.

Future Work

Our future efforts revolve around building probes unique to other molecular targets and expanding from conventional fluorescence to aggregation-induced emission.

Relevant Papers

Cheng Y, Borum RM, Clark AE, Jin Z, Moore C, Fajtova P, O'Donoghue AJ, Carlin AF, Jokerst JV. A dual-color fluorescent probe allows simultaneous imaging of main and papain-like proteases of SARS-CoV-2-infected cells for accurate detection and rapid inhibitor screening. Angewandte Chemie International Edition 2022, 61(9): 1-8. [Link]

Cheng Y, Clark AE, Zhou J, He T, Li Y, Borum RM, Creyer MN, Xu M, Jin Z, Zhou J, Yim W, Wu Z, Fajtova P, O'Donoghue AJ, Carlin AF, Jokerst JV. Protease-responsive peptide conjugated mitochondrial-targeting AlEgens for selective imaging and inhibition of SARS-CoV-2-infected cells, ACS Nano 2022, 16(8): 12305-12317. [Link]

Cheng Y, Clark AE, Yim W, Borum RM, Chang YC, Jin Z, He T, Carlin AF, Jokerst JV. Protease-responsive potential-tunable AIEgens for cell selective imaging of TMPRSS2 and accurate inhibitor screening. Analytical Chemistry 2023, 95(7): 3789–3798. [Link]