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Cam EFLS A. J. Kabla

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Collective migration of cell populations


Collective migration model

A number of biological processes, such as embryo development, cancer metastasis or wound healing, rely on cells moving in concert. The mechanisms leading to the emergence of group motion remain largely unexplored. Although biomolecular signalling is known to be involved in most occurrences of collective migration, the role of physical and mechanical interactions has been so far poorly addressed. In this work, a simple framework for cell motility is implemented in-silico in order to study the minimal requirements for the coordination of a group of epithelial cells, either as a spontaneously emerging behaviour, or as a response to "leader" cells. It appears that a key parameter, essentially characterising the ratio between the cohesion of the tissue and the motile force of individual cells, has the ability to control a wide spectrum of behaviours, from the epithelial-mesenchymal transition to the onset of collective invasion in cancer metastasis. This unified picture allows us to reassess the role of biomolecular signalling in a broader context and suggest a novel mechanism for driving cell sorting in remodelling tissues.

References:
Collective Cell Migration: Leadership, Invasion and Segregation
Alexandre J. Kabla
J. R. Soc. Interface, 9:3268-3278, 2012


Collective migration in confined environments

The role of geometrical confinement on collective cell migration has been recognized but has not been elucidated yet. We show that the geometrical properties of the environment regulate the formation of collective cell migration patterns through cell–cell interactions. Using microfabrication techniques to allow epithelial cell sheets to migrate into patterns of controlled geometries. In strips whose width was varied from one up to several cell diameters, we identified that the width of the channel influences the overall coordination of the cell displacements. In fact, if the population is confined in a geometry narrower than the correlation length of its velocity field measured in unconfined conditions, then the whole population exhibits a strongly coordinated mode of migration. This has been confirmed in other geometries, in particular disks.

References:
Emerging modes of collective cell migration induced by geometrical constraints
Sri Ram Krishna Vedula, Man Chun Leong, Tan Lei Laic, Pascal Hersen, Alexandre J. Kabla, Chwee Teck Lim and Benoit Ladoux
PNAS 109:12974-12979 (2012)
Guidance of collective cell migration by substrate geometry
K. Doxzen, S.R. Vedula, M.C. Leong, H. Hirata, N.S. Gov, A.J. Kabla, B. Ladoux and C.T. Lim
Integr. Biol., 5:1026-1035 (2013)

Guidance signal propagation in collectively migrating cell populations

Group cell migration in response to guidance signals is a critical process in determining tissue organization. Here we explore the response of groups of cells to topographic guidance signals and reveal that guidance information can be transmitted between cells within the group. Significantly, we show that guidance information transmission is not dependent on cell–cell junctions or tensional forces within cells. Instead, we propose that signal transmission arises from a volume exclusion-type mechanism and is an emergent property that can arise in dense cell populations.


References:
Non-autonomous contact guidance signaling during collective cell migration
Camila Londono, M. Jimena Loureiro, Benjamin Slater, Petra B. Lucker, John Soleas, Suthamathy Sathananthan, J. Stewart Aitchison, Alexandre Kabla, Alison P. McGuigan
PNAS 111:1807-1812 (2014).

Migration of Dictyostelium slugs

Work in collaboration with Pascal Hersen and Jean-Marc Di Meglio, Universite Denis Diderot, Paris. We currently study the migration of Dictyostelium slugs in confined and unconfined environments.

References:
In preparation.