Rapid, deep and precise profiling of the plasma proteome with multi-nanoparticle protein corona.

Nature Communications
John E BlumeOmid C Farokhzad

Abstract

Large-scale, unbiased proteomics studies are constrained by the complexity of the plasma proteome. Here we report a highly parallel protein quantitation platform integrating nanoparticle (NP) protein coronas with liquid chromatography-mass spectrometry for efficient proteomic profiling. A protein corona is a protein layer adsorbed onto NPs upon contact with biofluids. Varying the physicochemical properties of engineered NPs translates to distinct protein corona patterns enabling differential and reproducible interrogation of biological samples, including deep sampling of the plasma proteome. Spike experiments confirm a linear signal response. The median coefficient of variation was 22%. We screened 43 NPs and selected a panel of 5, which detect more than 2,000 proteins from 141 plasma samples using a 96-well automated workflow in a pilot non-small cell lung cancer classification study. Our streamlined workflow combines depth of coverage and throughput with precise quantification based on unique interactions between proteins and NPs engineered for deep and scalable quantitative proteomic studies.

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Citations

Aug 23, 2020·International Journal of Molecular Sciences·Nicolai Bjødstrup PalstrømHans Christian Beck
Oct 21, 2020·Nature Reviews. Materials·Zhongmin TangWei Tao
Oct 8, 2020·Biomedical Chromatography : BMC·Edouard C Nice
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Feb 23, 2021·Nano Letters·Yuxiu ChuChangyou Zhan
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May 6, 2021·Journal of the American Society for Mass Spectrometry·Xinyue LiuJoao A Paulo
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Jun 18, 2021·Proteomics·David W Greening, Richard J Simpson
Aug 4, 2021·Langmuir : the ACS Journal of Surfaces and Colloids·Jacob G Turner, Catherine J Murphy
Nov 13, 2020·Accounts of Chemical Research·Yuan LiuOmid C Farokhzad
Jul 7, 2021·Nature Materials·Irene de Lázaro, David J Mooney
Oct 22, 2021·Journal of Proteome Research·Eric W DeutschJochen M Schwenk
Nov 9, 2021·Advanced Healthcare Materials·Isabel GessnerRalph Weissleder

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Methods Mentioned

BETA
immunodepletion
membrane filtration
scanning
dynamic
transmission
X-ray
ELISA
Dynamic light scattering
electron microscopy
peptide assay

Software Mentioned

R scripts
tidyverse
PASEF
MaxLFQ
DIA
PRIDE
Perseus
MaxQuant
BoxCar
R

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