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

BMC Systems Biology
Heinrich J HuberMarkus Rehm

Abstract

Apoptosis is an essential cell death process throughout the entire life span of all metazoans and its deregulation in humans has been implicated in many proliferative and degenerative diseases. Mitochondrial outer membrane permeabilisation (MOMP) and activation of effector caspases are key processes during apoptosis signalling. MOMP can be subject to spatial coordination in human cancer cells, resulting in intracellular waves of cytochrome-c release. To investigate the consequences of these spatial anisotropies in mitochondrial permeabilisation on subsequent effector caspase activation, we devised a mathematical reaction-diffusion model building on a set of partial differential equations. Reaction-diffusion modelling suggested that even if strong spatial anisotropies existed during mitochondrial cytochrome c release, these would be eliminated by free diffusion of the cytosolic proteins that instantiate the apoptosis execution network. Experimentally, rapid sampling of mitochondrial permeabilisation and effector caspase activity in individual HeLa cervical cancer cells confirmed predictions of the reaction-diffusion model and demonstrated that the signalling network of apoptosis execution could efficiently translate spatial anis...Continue Reading

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Citations

Sep 1, 2012·Cell Death and Differentiation·A J García-Sáez
Jan 31, 2014·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Heinrich J HuberJochen H M Prehn
Jan 30, 2013·Journal of Mathematical Biology·Fernando López-CaamalHeinrich J Huber
Mar 3, 2011·Molecular Systems Biology·Heinrich J HuberJochen H M Prehn
Oct 19, 2010·Biochimica Et Biophysica Acta·Heinrich J HuberJochen H M Prehn
Nov 14, 2019·BMC Cancer·Manuela SalvucciJochen H M Prehn

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Methods Mentioned

BETA
FRET
fluorescence resonance

Software Mentioned

MOMP
MatLab
MatLab script
MetaMorph

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