Chemotaxis: a feedback-based computational model robustly predicts multiple aspects of real cell behaviour

Neilson, M. P., Veltman, D. M., van Haastert, P. J. M., Webb, S. D., Mackenzie, J. A. and Insall, R. H. (2011) Chemotaxis: a feedback-based computational model robustly predicts multiple aspects of real cell behaviour. PLoS Biology, 9(5), e1000618. (doi:10.1371/journal.pbio.1000618)

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Publisher's URL: http://dx.doi.org/10.1371/journal.pbio.1000618

Abstract

The mechanism of eukaryotic chemotaxis remains unclear despite intensive study. The most frequently described mechanism acts through attractants causing actin polymerization, in turn leading to pseudopod formation and cell movement. We recently proposed an alternative mechanism, supported by several lines of data, in which pseudopods are made by a self-generated cycle. If chemoattractants are present, they modulate the cycle rather than directly causing actin polymerization. The aim of this work is to test the explanatory and predictive powers of such pseudopod-based models to predict the complex behaviour of cells in chemotaxis. We have now tested the effectiveness of this mechanism using a computational model of cell movement and chemotaxis based on pseudopod autocatalysis. The model reproduces a surprisingly wide range of existing data about cell movement and chemotaxis. It simulates cell polarization and persistence without stimuli and selection of accurate pseudopods when chemoattractant gradients are present. It predicts both bias of pseudopod position in low chemoattractant gradients and-unexpectedly-lateral pseudopod initiation in high gradients. To test the predictive ability of the model, we looked for untested and novel predictions. One prediction from the model is that the angle between successive pseudopods at the front of the cell will increase in proportion to the difference between the cell's direction and the direction of the gradient. We measured the angles between pseudopods in chemotaxing Dictyostelium cells under different conditions and found the results agreed with the model extremely well. Our model and data together suggest that in rapidly moving cells like Dictyostelium and neutrophils an intrinsic pseudopod cycle lies at the heart of cell motility. This implies that the mechanism behind chemotaxis relies on modification of intrinsic pseudopod behaviour, more than generation of new pseudopods or actin polymerization by chemoattractants

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Neilson, Dr Matthew and Insall, Professor Robert
Authors: Neilson, M. P., Veltman, D. M., van Haastert, P. J. M., Webb, S. D., Mackenzie, J. A., and Insall, R. H.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:PLoS Biology
Publisher:Public Library of Science
ISSN:1544-9173
ISSN (Online):1545-7885
Copyright Holders:Copyright © 2011 The Authors
First Published:First published in PLoS Biology 9(5):e1000618
Publisher Policy:Reproduced in accordance with the copyright policy of the publisher
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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
506871Computational modelling of cell movement and chemotaxisRobert InsallMedical Research Council (MRC)G0802579Beatson Institute for Cancer Research