Analysis of the influence of cell heterogeneity on nanoparticle dose response

Matthew J. Ware, Biana Godin, Neenu Singh, Ravish Majithia, Sabeel Shamsudeen, Rita Serda, Kenith E. Meissner, Paul Rees, Huw Summers

Research output: Contribution to journalArticlepeer-review

31 Scopus citations


Understanding the effect of variability in the interaction of individual cells with nanoparticles on the overall response of the cell population to a nanoagent is a fundamental challenge in bionanotechnology. Here, we show that the technique of time-resolved, high-throughput microscopy can be used in this endeavor. Mass measurement with single-cell resolution provides statistically robust assessments of cell heterogeneity, while the addition of a temporal element allows assessment of separate processes leading to deconvolution of the effects of particle supply and biological response. We provide a specific demonstration of the approach, in vitro, through time-resolved measurement of fibroblast cell (HFF-1) death caused by exposure to cationic nanoparticles. The results show that heterogeneity in cell area is the major source of variability with area-dependent nanoparticle capture rates determining the time of cell death and hence the form of the exposure-response characteristic. Moreover, due to the particulate nature of the nanoparticle suspension, there is a reduction in the particle concentration over the course of the experiment, eventually causing saturation in the level of measured biological outcome. A generalized mathematical description of the system is proposed, based on a simple model of particle depletion from a finite supply reservoir. This captures the essential aspects of the nanoparticle-cell interaction dynamics and accurately predicts the population exposure-response curves from individual cell heterogeneity distributions.

Original languageEnglish (US)
Pages (from-to)6693-6700
Number of pages8
JournalACS Nano
Issue number7
StatePublished - Jul 22 2014


  • bionanotechnology
  • dose-response characteristic
  • high-throughput microscopy
  • nanomedicine
  • nanoparticle dose
  • nanoparticle exposure
  • nanotoxicology

ASJC Scopus subject areas

  • Engineering(all)
  • Materials Science(all)
  • Physics and Astronomy(all)


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