BMC Systems Biology

official impact factor 3.57

Open Access Research article

Diffusion is capable of translating anisotropic apoptosis initiation into a homogeneous execution of cell death

Heinrich J Huber1,2*, Maike A Laussmann1, Jochen HM Prehn1 and Markus Rehm1*

Author Affiliations

1 Sytems Biology Group, Department of Physiology & Medical Physics, Royal College of Surgeons in Ireland, Dublin 2, Ireland

2 Siemens Ireland, Leeson Close, Dublin 2, Ireland

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BMC Systems Biology 2010, 4:9 doi:10.1186/1752-0509-4-9

Published: 4 February 2010

Additional files

Additional file 1:

Modelling parameters for the reaction-diffusion model. These additional tables list the state variables of the model (Table S1), the individual reactions and reaction constants including literature references (Table S2), molecular masses of all reactants (Table S3), and the biochemical reaction rates (Table S4).

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Additional file 2:

Comparison of diffusive signal spread between simplified one and three dimensional scenarios. Comparison of signal spread between simplified one and a three dimensional spatial models. The one dimensional model represents a linear slab with the input pulse located at the left boundary (A). The three dimensional model represents a sphere with the input signal starting synchronously on the entire surface of the sphere (B). Signal progression along the slab (1 dimensional model) or towards the centre of the sphere (3 dimensional model) was investigated. To mathematically handle the 3-dimensional spherical model with the PDEPE subroutine in MATLAB, the diffusion process was transformed to a problem of one spatial and temporal component without loss of information. This yielded the following reaction diffusion equation for the radial component of species n:

where r is the radius and Dn denotes the diffusion coefficient. Only small discrepancies were observed between the two scenarios. More complex scenarios such as spatially anisotropic triggers could not be subjected to this dimension reduction.

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Additional file 3:

Spatial progression of mitochondrial permeabilisation. A movie of a representative HeLa cervical cancer cell expressing a red fluorescent reporter protein targeted to the mitochondrial intermembrane space (IMS-RP) is shown. Release of IMS-RP results in a drop in fluorescence intensity. Following treatment with 1 μg/ml TRAIL/CHX, IMS-RP release is first initiated on the left side and progresses through the cell body until the release is complete. The movie represents a duration of 5.25 min.

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Additional file 4:

Spatially homogeneous caspase activation in HeLa cervical cancer cells. Substrate cleavage by effector caspases was experimentally measured by CFP-DEVD-YFP FRET disruption at fast sampling rates in HeLa cells. FRET disruption was measured in regions at distal ends of the cell. The traces shown were obtained from a cell treated with 100 ng/ml TRAIL/1 μg/ml CHX. Arrow indicates onset of substrate cleavage. Corresponding results were obtained from n = 19 additional cells treated with TRAIL/CHX and n = 14 cells treated with 1 μM STS.

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Additional file 5:

MatLab script of the reaction-diffusion model. The file contains the MatLab code for the reaction-diffusion model and the required annotations to repeat all modelling presented in this study. The model could not be provided as SBML as spatiotemporal PDE models are not yet supported.

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Additional file 6:

Photobleaching control measurement for rapid FRET sampling. Fluorescence signal intensities in CFP, FRET, and YFP channels were measured in unstimulated cells at rapid sampling conditions. This control excludes that photodamage by the acquisition process influenced the experimental measurements of effector caspase activation.

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