» Articles » PMID: 35275789

Engineered Nanoparticles Enable Deep Proteomics Studies at Scale by Leveraging Tunable Nano-bio Interactions

Abstract

SignificanceDeep profiling of the plasma proteome at scale has been a challenge for traditional approaches. We achieve superior performance across the dimensions of precision, depth, and throughput using a panel of surface-functionalized superparamagnetic nanoparticles in comparison to conventional workflows for deep proteomics interrogation. Our automated workflow leverages competitive nanoparticle-protein binding equilibria that quantitatively compress the large dynamic range of proteomes to an accessible scale. Using machine learning, we dissect the contribution of individual physicochemical properties of nanoparticles to the composition of protein coronas. Our results suggest that nanoparticle functionalization can be tailored to protein sets. This work demonstrates the feasibility of deep, precise, unbiased plasma proteomics at a scale compatible with large-scale genomics enabling multiomic studies.

Citing Articles

Protein Corona of Nanoparticles: Isolation and Analysis.

Sun Y, Zhou Y, Rehman M, Wang Y, Guo S Chem Bio Eng. 2025; 1(9):757-772.

PMID: 39974182 PMC: 11792916. DOI: 10.1021/cbe.4c00105.


The Circulating Proteome─Technological Developments, Current Challenges, and Future Trends.

Geyer P, Hornburg D, Pernemalm M, Hauck S, Palaniappan K, Albrecht V J Proteome Res. 2024; 23(12):5279-5295.

PMID: 39479990 PMC: 11629384. DOI: 10.1021/acs.jproteome.4c00586.


A plasma proteomic signature links secretome of senescent monocytes to aging- and obesity-related clinical outcomes in humans.

Olinger B, Banarjee R, Dey A, Tsitsipatis D, Tanaka T, Ram A medRxiv. 2024; .

PMID: 39371126 PMC: 11451660. DOI: 10.1101/2024.08.01.24311368.


Designing nanotheranostics with machine learning.

Rao L, Yuan Y, Shen X, Yu G, Chen X Nat Nanotechnol. 2024; 19(12):1769-1781.

PMID: 39362960 DOI: 10.1038/s41565-024-01753-8.


Deep Profiling of Plasma Proteoforms with Engineered Nanoparticles for Top-Down Proteomics.

Huang C, Hollas M, Sanchez A, Bhattacharya M, Ho G, Sundaresan A J Proteome Res. 2024; 23(10):4694-4703.

PMID: 39312774 PMC: 11789057. DOI: 10.1021/acs.jproteome.4c00621.


References
1.
Lundqvist M, Stigler J, Elia G, Lynch I, Cedervall T, Dawson K . Nanoparticle size and surface properties determine the protein corona with possible implications for biological impacts. Proc Natl Acad Sci U S A. 2008; 105(38):14265-70. PMC: 2567179. DOI: 10.1073/pnas.0805135105. View

2.
Geyer P, Holdt L, Teupser D, Mann M . Revisiting biomarker discovery by plasma proteomics. Mol Syst Biol. 2017; 13(9):942. PMC: 5615924. DOI: 10.15252/msb.20156297. View

3.
Kulak N, Geyer P, Mann M . Loss-less Nano-fractionator for High Sensitivity, High Coverage Proteomics. Mol Cell Proteomics. 2017; 16(4):694-705. PMC: 5383787. DOI: 10.1074/mcp.O116.065136. View

4.
Wang Y, Cai R, Chen C . The Nano-Bio Interactions of Nanomedicines: Understanding the Biochemical Driving Forces and Redox Reactions. Acc Chem Res. 2019; 52(6):1507-1518. DOI: 10.1021/acs.accounts.9b00126. View

5.
Dawson N, Lewis T, Das S, Lees J, Lee D, Ashford P . CATH: an expanded resource to predict protein function through structure and sequence. Nucleic Acids Res. 2016; 45(D1):D289-D295. PMC: 5210570. DOI: 10.1093/nar/gkw1098. View