What is actomyosin cortex?
The cell cortex is a thin (~0.1 µm thick) network of actin filaments and actin-binding proteins that underlies the plasma membrane in most eukaryotic cells. The cortex is the main determinant of cell shape and therefore plays a fundamental role in processes such as cell division, migration, and tissue morphogenesis. Despite its importance, our knowledge of the molecular and biophysical mechanisms underlying cortical formation and function is poor.
Previous work in the lab
In recent years, work in the lab has focused on identifying the proteins that nucleate actin filaments in the cellular cortex and on measuring the cortical actin filament dynamics and length distribution. We have identified two proteins that generate the bulk of the cortical actin: the formin Diaph1 and the Arp2/3 complex. The very different kinetics of assembly of both networks suggests that cells can rapidly fine-tune cortex structure and mechanics by adjusting the relative contribution of each nucleator [1, 2]. Furthermore, by using photobleaching experiments and mathematical modelling, we showed that the presence of two nucleators with different polymerisation kinetics is sufficient to qualitatively and quantitatively reproduce our experimental observation [3, 4].
(A) Cell cortex of a HeLa cell. (B) Cortex is a meshwork (~ 30 nm mesh size) of F-actin filaments crosslinked by actin-bundling proteins. (C) Theoretical descriptions of the actin cortex predict that cortical mechanics are governed by the length distribution of polymer chains, the distance between and nature of crosslinkers and the density of motor proteins.
Currently in the lab
Our work currently focuses on investigating what proteins regulate nucleator activity of the actin nucleators, how each of the two actin nucleators contribute to cortical mechanics and what structural proteins participate in setting cortical mechanics.
Relevant publications:
[1] Bovellan, M., Romeo, Y., Biro, M., Boden, A., Chugh, P., Yonis, A., Vaghela, M., Fritzsche, M., Moulding, D., Thorogate, R., Jégou, A.,Thrasher, A.J., Romet-Lemonne, G., Roux, P.P., Paluch, E.K. & Charras, G., 2014. Cellular control of cortical actin nucleation. Current Biology, 24(14), pp.1628-1635.
[2] Biro, M., Romeo, Y., Kroschwald, S., Bovellan, M., Boden, A., Tcherkezian, J., Roux, P.P., Charras, G. and Paluch, E.K., 2013. Cell cortex composition and homeostasis resolved by integrating proteomics and quantitative imaging. Cytoskeleton, 70(11), pp.741-754.
[3] Fritzsche, M., Lewalle, A., Duke, T., Kruse, K. and Charras, G., 2013. Analysis of turnover dynamics of the submembranous actin cortex. Molecular biology of the cell, 24(6), pp.757-767.
[4] Fritzsche, M., Erlenkämper, C., Moeendarbary, E., Charras, G. and Kruse, K., 2016. Actin kinetics shapes cortical network structure and mechanics. Science advances, 2(4), p.e1501337.
Collaborators on this project:
Ewa Paluch (LMCB, UCL, London, UK)
Philippe Roux (IRIC, Universite de Montreal, Canada)
Guillaume Romet-Lemonne (Institut Jacques Monod, France)
Guillaume Salbreux (Crick Institute, London, UK)
Funding on this project:
Human Frontiers of Science Program Young investigator grants
Cancer Research UK – Multidisciplinary project award
Charras Lab 