Elastomeric sensor surfaces for high-Throughput single-cell force cytometry

Ivan Pushkarsky, Peter Tseng, Dylan Black, Bryan France, Lyndon Warfe, Cynthia J. Koziol-White, William F. Jester, Ryan K. Trinh, Jonathan Lin, Philip O. Scumpia, Sherie L. Morrison, Reynold A. Panettieri, Robert Damoiseaux, Dino Di Carlo

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

Abstract

As cells with aberrant force-generating phenotypes can directly lead to disease, cellular force-generation mechanisms are high-value targets for new therapies. Here, we show that single-cell force sensors embedded in elastomers enable single-cell force measurements with ~100-fold improvement in throughput than was previously possible. The microtechnology is scalable and seamlessly integrates with the multi-well plate format, enabling highly parallelized time-course studies. In this regard, we show that airway smooth muscle cells isolated from fatally asthmatic patients have innately greater and faster force-generation capacity in response to stimulation than healthy control cells. By simultaneously tracing agonist-induced calcium flux and contractility in the same cell, we show that the calcium level is ultimately a poor quantitative predictor of cellular force generation. Finally, by quantifying phagocytic forces in thousands of individual human macrophages, we show that force initiation is a digital response (rather than a proportional one) to the proper immunogen. By combining mechanobiology at the single-cell level with high-Throughput capabilities, this microtechnology can support drug-discovery efforts for clinical conditions associated with aberrant cellular force generation.

Original languageEnglish (US)
Pages (from-to)124-137
Number of pages14
JournalNature biomedical engineering
Volume2
Issue number2
DOIs
StatePublished - Feb 1 2018

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Bioengineering
  • Medicine (miscellaneous)
  • Biomedical Engineering
  • Computer Science Applications

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