Mohammed, D;
Charras, G;
Vercruysse, E;
Versaevel, M;
Lantoine, J;
Alaimo, L;
Bruyère, C;
... Gabriele, S; + view all
(2019)
Substrate area confinement is a key determinant of cell velocity in collective migration.
Nature Physics
, 15
pp. 858-866.
10.1038/s41567-019-0543-3.
Preview |
Text
Charras Mohammed_revised_3rd_2019_cut.pdf - Accepted Version Download (1MB) | Preview |
Abstract
Collective cell migration is fundamental throughout development, during wound healing and in many diseases. Although much effort has focused on cell–cell junctions, a role for physical confinement in collective cell migration remains unclear. Here, we used adhesive microstripes of varying widths to mimic the spatial confinement experienced by follower cells within epithelial tissues. Our results reveal that the substrate area confinement is sufficient to modulate the three-dimensional cellular morphology without the need for intercellular adhesive cues. Our findings show a direct correlation between the migration velocity of confined cells and their cell–substrate adhesive area. Closer examination revealed that adhesive area confinement reduces lamellipodial protrusive forces, decreases the number of focal complexes at the leading edge and prevents the maturation of focal adhesions at the trailing edge, together leading to less effective forward propelling forces. The release of follower confinement required for the emergence of leader cells is associated with a threefold increase in contractile stress and a tenfold increase in protrusive forces, together providing a sufficient stress to generate highly motile mesenchymal cells. These findings demonstrate that epithelial confinement alone can induce follower-like behaviours and identify substrate adhesive area confinement as a key determinant of cell velocity in collective migration.
| Type: | Article |
|---|---|
| Title: | Substrate area confinement is a key determinant of cell velocity in collective migration |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1038/s41567-019-0543-3 |
| Publisher version: | https://doi.org/10.1038/s41567-019-0543-3 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | Biological physics, Cellular motility, Motility |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > UCL BEAMS UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences > London Centre for Nanotechnology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10077900 |
Archive Staff Only
 |
View Item |
