High-Throughput Mechanobiology Screening Platform Using Micro- and Nanotopography

Junqiang Hu, Alexander A. Gondarenko, Alex P. Dang, Keenan T. Bashour, Roddy S. O'Connor, Sunwoo Lee, Anastasia Liapis, Saba Ghassemi, Michael C. Milone, Michael P. Sheetz, Michael L. Dustin, Lance C. Kam, James C. Hone

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

We herein demonstrate the first 96-well plate platform to screen effects of micro- and nanotopographies on cell growth and proliferation. Existing high-throughput platforms test a limited number of factors and are not fully compatible with multiple types of testing and assays. This platform is compatible with high-throughput liquid handling, high-resolution imaging, and all multiwell plate-based instrumentation. We use the platform to screen for topographies and drug-topography combinations that have short- and long-term effects on T cell activation and proliferation. We coated nanofabricated "trench-grid" surfaces with anti-CD3 and anti-CD28 antibodies to activate T cells and assayed for interleukin 2 (IL-2) cytokine production. IL-2 secretion was enhanced at 200 nm trench width and >2.3 μm grating pitch; however, the secretion was suppressed at 100 nm width and <0.5 μm pitch. The enhancement on 200 nm grid trench was further amplified with the addition of blebbistatin to reduce contractility. The 200 nm grid pattern was found to triple the number of T cells in long-term expansion, a result with direct clinical applicability in adoptive immunotherapy.

Original languageEnglish (US)
Pages (from-to)2198-2204
Number of pages7
JournalNano Letters
Volume16
Issue number4
DOIs
StatePublished - Apr 13 2016

Keywords

  • High-throughput screening
  • Lck
  • T cell
  • interleukin-2
  • long-term expansion
  • nanotechnology

ASJC Scopus subject areas

  • Bioengineering
  • Chemistry(all)
  • Materials Science(all)
  • Condensed Matter Physics
  • Mechanical Engineering

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