dictyNews
Electronic Edition
Volume 49, number 10
April 7, 2023

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Abstracts
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Competition between chemoattractants causes unexpected 
complexityand can explain negative chemotaxis

Adam Dowdell,  Peggy Paschke, Peter Thomason, Luke Tweedy  
and Robert H. Insall


Published Current Biology
https://europepmc.org/article/PPR/PPR582418

Negative chemotaxis, where eukaryotic cells migrate away from 
repellents, is important throughout biology, for example, in 
nervous system patterning and resolution of inflammation. However, 
the mechanisms by which molecules repel migrating cells are 
unknown. Here, we use predictive modeling and experiments with 
Dictyostelium cells to show that competition between different 
ligands that bind to the same receptor leads to effective 
chemorepulsion. 8-CPT-cAMP, widely described as a simple 
chemorepellent, is inactive on its own and only repels cells when 
it acts in combination with the attractant cAMP. If cells degrade 
either competing ligand, the pattern of migration becomes more 
complex; cells may be repelled in one part of a gradient but 
attracted elsewhere, leading to populations moving in different 
directions in the same assay or converging in an arbitrary place. 
More counterintuitively still, two chemicals that normally attract cells 
can become repellent when combined. Computational models of 
chemotaxis are now accurate enough to predict phenomena that 
have not been anticipated by experiments. We have used them to 
identify new mechanisms that drive reverse chemotaxis, which we 
have confirmed through experiments with real cells. These findings 
are important whenever multiple ligands compete for the same 
receptors.


Submitted by Robert Insall [[log in to unmask]]
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