Unbiased phosphoproteomic method identifies the initial effects of a methacrylic acid copolymer on macrophages

Michael Dean Chamberlain; Laura A Wells; Alexandra Lisovsky; Hongbo Guo; Ruth Isserlin; Ilana Talior-Volodarsky; Redouan Mahou; Andrew Emili; Michael V Sefton

doi:10.1073/pnas.1508826112

Unbiased phosphoproteomic method identifies the initial effects of a methacrylic acid copolymer on macrophages

Proc Natl Acad Sci U S A. 2015 Aug 25;112(34):10673-8. doi: 10.1073/pnas.1508826112. Epub 2015 Aug 10.

Authors

Michael Dean Chamberlain¹, Laura A Wells¹, Alexandra Lisovsky¹, Hongbo Guo², Ruth Isserlin², Ilana Talior-Volodarsky¹, Redouan Mahou¹, Andrew Emili², Michael V Sefton³

Affiliations

¹ Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, ON, Canada M5S 3G9;
² Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, Canada M5S 3G9;
³ Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, ON, Canada M5S 3G9; Department of Chemical Engineering and Applied Chemistry, University of Toronto, Toronto, ON, Canada M5S 3G9 michael.sefton@utoronto.ca.

Abstract

An unbiased phosphoproteomic method was used to identify biomaterial-associated changes in the phosphorylation patterns of macrophage-like cells. The phosphorylation differences between differentiated THP1 (dTHP1) cells treated for 10, 20, or 30 min with a vascular regenerative methacrylic acid (MAA) copolymer or a control methyl methacrylate (MM) copolymer were determined by MS. There were 1,470 peptides (corresponding to 729 proteins) that were differentially phosphorylated in dTHP1 cells treated with the two materials with a greater cellular response to MAA treatment. In addition to identifying pathways (such as integrin signaling and cytoskeletal arrangement) that are well known to change with cell-material interaction, previously unidentified pathways, such as apoptosis and mRNA splicing, were also discovered.

Keywords: macrophage; material–cell interactions; methacrylic acid; phosphoproteomic.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adsorption
Apoptosis Regulatory Proteins / metabolism
Biocompatible Materials / pharmacology*
Cell Adhesion Molecules / metabolism
Cell Line, Tumor
Cytoskeletal Proteins / metabolism
Gene Expression Profiling*
Humans
Intracellular Signaling Peptides and Proteins / metabolism
Macrophages / chemistry
Macrophages / drug effects*
Materials Testing
Membrane Proteins / metabolism
Methylmethacrylate
Neoplasm Proteins / metabolism
Phosphoprotein Phosphatases / metabolism
Phosphoproteins / analysis*
Phosphorylation
Polymethacrylic Acids / pharmacology*
Protein Kinases / metabolism
Protein Processing, Post-Translational / drug effects*
Proteomics / methods*
Transcription Factors / metabolism

Substances

Apoptosis Regulatory Proteins
Biocompatible Materials
Cell Adhesion Molecules
Cytoskeletal Proteins
Intracellular Signaling Peptides and Proteins
Membrane Proteins
Neoplasm Proteins
Phosphoproteins
Polymethacrylic Acids
Transcription Factors
Methylmethacrylate
Protein Kinases
Phosphoprotein Phosphatases

Grants and funding

Canadian Institutes of Health Research/Canada