Tissue matrix arrays for high-throughput screening and systems analysis of cell function

Vince Z. Beachley, Matthew T. Wolf, Kaitlyn Sadtler, Srikanth S. Manda, Heather Jacobs, Michael R. Blatchley, Joel S. Bader, Akhilesh Pandey, Drew Pardoll, Jennifer H. Elisseeff

Research output: Contribution to journalArticle

78 Scopus citations

Abstract

Cell and protein arrays have demonstrated remarkable utility in the high-throughput evaluation of biological responses; however, they lack the complexity of native tissue and organs. Here we spotted tissue extracellular matrix (ECM) particles as two-dimensional (2D) arrays or incorporated them with cells to generate three-dimensional (3D) cell-matrix microtissue arrays. We then investigated the responses of human stem, cancer and immune cells to tissue ECM arrays originating from 11 different tissues. We validated the 2D and 3D arrays as representative of the in vivo microenvironment by means of quantitative analysis of tissue-specific cellular responses, including matrix production, adhesion and proliferation, and morphological changes after culture. The biological outputs correlated with tissue proteomics, and network analysis identified several proteins linked to cell function. Our methodology enables broad screening of ECMs to connect tissue-specific composition with biological activity, providing a new resource for biomaterials research and further understanding of regeneration and disease mechanisms.

Original languageEnglish (US)
Pages (from-to)1197-1204
Number of pages8
JournalNature Methods
Volume12
Issue number12
DOIs
StatePublished - Dec 1 2015

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Beachley, V. Z., Wolf, M. T., Sadtler, K., Manda, S. S., Jacobs, H., Blatchley, M. R., Bader, J. S., Pandey, A., Pardoll, D., & Elisseeff, J. H. (2015). Tissue matrix arrays for high-throughput screening and systems analysis of cell function. Nature Methods, 12(12), 1197-1204. https://doi.org/10.1038/nmeth.3619