title: Directional collective cell migration emerges as a property of cell interactions.
abstract: Collective cell migration is a fundamental process, occurring during embryogenesis and cancer metastasis. Neural crest cells exhibit such coordinated migration, where aberrant motion can lead to fatality or dysfunction of the embryo. Migration involves at least two complementary mechanisms: contact inhibition of locomotion (a repulsive interaction corresponding to a directional change of migration upon contact with a reciprocating cell), and co-attraction (a mutual chemoattraction mechanism). Here, we develop and employ a parameterized discrete element model of neural crest cells, to investigate how these mechanisms contribute to long-range directional migration during development. Motion is characterized using a coherence parameter and the time taken to reach, collectively, a target location. The simulated cell group is shown to switch from a diffusive to a persistent state as the response-rate to co-attraction is increased. Furthermore, the model predicts that when co-attraction is inhibited, neural crest cells can migrate into restrictive regions. Indeed, inhibition of co-attraction in vivo and in vitro leads to cell invasion into restrictive areas, confirming the prediction of the model. This suggests that the interplay between the complementary mechanisms may contribute to guidance of the neural crest. We conclude that directional migration is a system property and does not require action of external chemoattractants.
authors.affiliation: Centre for Mathematics and Physics in the Life Sciences and Experimental Biology, University College London, London, United Kingdom; Department of Cell and Developmental Biology, University College London, London, United Kingdom; Department of Mathematics, University College London, London, United Kingdom.
authors.forename: Mae L
authors.initials: ML
authors.lastname: Woods
authors.affiliation: Department of Cell and Developmental Biology, University College London, London, United Kingdom.
authors.forename: Carlos
authors.initials: C
authors.lastname: Carmona-Fontaine
authors.affiliation: Department of Cell and Developmental Biology, University College London, London, United Kingdom.
authors.forename: Chris P
authors.initials: CP
authors.lastname: Barnes
authors.affiliation: Department of Ecology and Evolutionary Biology, Princeton University, Princeton, New Jersey, United States of America.
authors.forename: Iain D
authors.initials: ID
authors.lastname: Couzin
authors.affiliation: Department of Cell and Developmental Biology, University College London, London, United Kingdom.
authors.forename: Roberto
authors.initials: R
authors.lastname: Mayor
authors.affiliation: Centre for Mathematics and Physics in the Life Sciences and Experimental Biology, University College London, London, United Kingdom; Department of Mathematics, University College London, London, United Kingdom.
authors.forename: Karen M
authors.initials: KM
authors.lastname: Page
mesh_terms: D000818:Animals; D002138:Calibration; D002450:Cell Communication; D002465:Cell Movement; D003260:Contact Inhibition; D008954:Models, Biological; D013997:Time Factors; D014981:Xenopus