Comprehensive proteomic analysis of mineral nanoparticles derived from human body fluids and analyzed by liquid chromatography-tandem mass spectrometry

Jan Martel, David Young, Andrew Young, Cheng Yeu Wu, Chi De Chen, Jau Song Yu, John D. Young*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

68 Scopus citations

Abstract

Mineralo-protein nanoparticles (NPs) formed spontaneously in the body have been associated with ectopic calcifications seen in atherosclerosis, chronic degenerative diseases, and kidney stone formation. Synthetic NPs are also known to become coated with proteins when they come in contact with body fluids. Identifying the proteins found in NPs should help unravel how NPs are formed in the body and how NPs in general, be they synthetic or naturally formed, interact within the body. Here, we developed a proteomic approach based on liquid chromatography (LC) and tandem mass spectrometry (MS/MS) to determine the protein composition of carbonate-apatite NPs derived from human body fluids (serum, urine, cerebrospinal fluid, ascites, pleural effusion, and synovial fluid). LC-MS/MS provided not only an efficient and comprehensive determination of the protein constituents, but also a semiquantitative ranking of the identified proteins. Notably, the identified NP proteins mirrored the protein composition of the contacting body fluids, with albumin, fetuin-A, complement C3, α-1-antitrypsin, prothrombin, and apolipoproteins A1 and B-100 being consistently associated with the particles. Since several coagulation factors, calcification inhibitors, complement proteins, immune regulators, protease inhibitors, and lipid/molecule carriers can all become NP constituents, our results suggest that mineralo-protein complexes may interface with distinct biochemical pathways in the body depending on their protein composition. We propose that LC-MS/MS be used to characterize proteins found in both synthetic and natural NPs.

Original languageEnglish
Pages (from-to)111-125
Number of pages15
JournalAnalytical Biochemistry
Volume418
Issue number1
DOIs
StatePublished - 01 11 2011

Keywords

  • Ectopic calcification
  • LC-MS/MS
  • Mineral nanoparticles
  • Protein corona
  • Proteomics

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