No Cover Image

Journal article 651 views 96 downloads

Analysis of the Influence of Cell Heterogeneity on Nanoparticle Dose Response / Matthew J. Ware, Biana Godin, Neenu Singh, Ravish Majithia, Sabeel Shamsudeen, Rita E. Serda, Kenith Meissner, Paul Rees, Huw Summers

ACS Nano, Volume: 8, Issue: 7, Pages: 6693 - 6700

Swansea University Authors: Neenu Singh, Kenith Meissner, Paul Rees, Huw Summers

Check full text

DOI (Published version): 10.1021/nn502356f

Abstract

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 i...

Full description

Published in: ACS Nano
ISSN: 1936-0851 1936-086X
Published: 2014
Online Access: Check full text

URI: https://cronfa.swan.ac.uk/Record/cronfa20184
Tags: Add Tag
No Tags, Be the first to tag this record!
Abstract: 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.
Item Description: ACS AuthorChoice - Terms of Use CC-BY
Keywords: bionanotechnology; dose−response characteristic; high-throughput microscopy; nanomedicine; nanoparticle dose; nanoparticle exposure; nanotoxicology
College: College of Engineering
Issue: 7
Start Page: 6693
End Page: 6700