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Open Access Methodology article

A transfer function approach to measuring cell inheritance

Paul Rees1*, M Rowan Brown1, Huw D Summers1, Mark D Holton1, Rachel J Errington2, Sally C Chappell2 and Paul J Smith2

Author Affiliations

1 Centre for Nanohealth, School of Engineering, Swansea University, Swansea, SA2 8PP, UK

2 School of Medicine, Cardiff University, Heath Park, Cardiff, CF14 4XN, UK

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BMC Systems Biology 2011, 5:31  doi:10.1186/1752-0509-5-31

Published: 22 February 2011

Abstract

Background

The inheritance of cellular material between parent and daughter cells during mitosis is highly influential in defining the properties of the cell and therefore the population lineage. This is of particular relevance when studying cell population evolution to assess the impact of a disease or the perturbation due to a drug treatment. The usual technique to investigate inheritance is to use time-lapse microscopy with an appropriate biological marker, however, this is time consuming and the number of inheritance events captured are too low to be statistically meaningful.

Results

Here we demonstrate the use of a high throughput fluorescence measurement technique e.g. flow cytometry, to measure the fluorescence from quantum dot markers which can be used to target particular cellular sites. By relating, the fluorescence intensity measured between two time intervals to a transfer function we are able to deconvolve the inheritance of cellular material during mitosis. To demonstrate our methodology we use CdTe/ZnS quantum dots to measure the ratio of endosomes inherited by the two daughter cells during mitosis in the U2-OS, human osteoscarcoma cell line. The ratio determined is in excellent agreement with results obtained previously using a more complex and computational intensive bespoke stochastic model.

Conclusions

The use of a transfer function approach allows us to utilise high throughput measurement of large cell populations to derive statistically relevant measurements of the inheritance of cellular material. This approach can be used to measure the inheritance of organelles, proteins etc. and also particles introduced to cells for drug delivery.