Local modulation of chemoattractant concentrations by single cells: dissection using a bulk-surface computational model

Mackenzie, J.A., Nolan, M. and Insall, R.H. (2016) Local modulation of chemoattractant concentrations by single cells: dissection using a bulk-surface computational model. Interface Focus, 6(5), 20160036. (doi: 10.1098/rsfs.2016.0036) (PMID:27708760) (PMCID:PMC4992739)

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Abstract

Chemoattractant gradients are usually considered in terms of sources and sinks that are independent of the chemotactic cell. However, recent interest has focused on ‘self-generated’ gradients, in which cell populations create their own local gradients as they move. Here, we consider the interplay between chemoattractants and single cells. To achieve this, we extend a recently developed computational model to incorporate breakdown of extracellular attractants by membrane-bound enzymes. Model equations are parametrized, using the published estimates from Dictyostelium cells chemotaxing towards cyclic AMP. We find that individual cells can substantially modulate their local attractant field under physiologically appropriate conditions of attractant and enzymes. This means the attractant concentration perceived by receptors can be a small fraction of the ambient concentration. This allows efficient chemotaxis in chemoattractant concentrations that would be saturating without local breakdown. Similar interactions in which cells locally mould a stimulus could function in many types of directed cell motility, including haptotaxis, durotaxis and even electrotaxis.

Item Type:Articles
Additional Information:M.N. gratefully acknowledges the financial support from the UK Engineering and Physical Sciences Research Council (EPSRC) and Cancer Research UK for a postgraduate studentship award. Core support for R.H.I was provided by Cancer Research UK, grant no. 15672. This work was completed while J.A.M. was a Leverhulme Trust Research Fellow, supported by the award RF-2014-522.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Insall, Professor Robert
Authors: Mackenzie, J.A., Nolan, M., and Insall, R.H.
College/School:College of Medical Veterinary and Life Sciences > School of Cancer Sciences
Journal Name:Interface Focus
Publisher:The Royal Society
ISSN:2042-8898
ISSN (Online):2042-8901
Published Online:19 August 2016
Copyright Holders:Copyright © 2016 The Authors
First Published:First published in Interface Focus 6(5): 20160036
Publisher Policy:Reproduced under a Creative Commons License
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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
303051Molecular recognition, subunit interaction & structure function analysis of Recombinant human and plant PDCsJohn Gordon LindsayBiotechnology and Biological Sciences Research Council (BBSRC)17/B15672RI MOLECULAR CELL & SYSTEMS BIOLOGY