Biology Inspired Physics at Mesoscales

Team Publications

Year of publication 2017

Vincent Hakim, Pascal Silberzan (2017 Mar 11)

Collective cell migration : a physics perspective.

Reports on progress in physics. Physical Society (Great Britain) : DOI : 10.1088/1361-6633/aa65ef Learn more
Summary

Cells have traditionally been viewed either as independently moving entities or as somewhat static parts of tissues. However, it is now clear that in many cases, multiple cells coordinate their motions and move as collective entities. Well-studied examples comprise development events, as well as physiological and pathological situations. Different ex vivo model systems have also been investigated. Several recent advances have taken place at the interface between biology and physics and have benefitted from the progress in imaging and microscopy, the use of microfabrication techniques, as well as the introduction of quantitative tools and models. We review these interesting developments in quantitative cell biology that also provide rich examples of collective out-of-equilibrium motion.

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Duclos G., Erlenkämper C., Joanny J.-F., Silberzan P. (2016 Sep 12)

Topological defects in confined populations of spindle-shaped cells

Nature Physics : 13 : 58-62 : DOI : 10.1038/nphys3876 Learn more
Summary

Most spindle-shaped cells (including smooth muscles and sarcomas) organize in vivo into well-aligned ‘nematic’ domains, creating intrinsic topological defects that may be used to probe the behaviour of these active nematic systems. Active non-cellular nematics have been shown to be dominated by activity, yielding complex chaotic flows. However, the regime in which live spindle-shaped cells operate, and the importance of cell–substrate friction in particular, remains largely unexplored. Using in vitro experiments, we show that these active cellular nematics operate in a regime in which activity is effectively damped by friction, and that the interaction between defects is controlled by the system’s elastic nematic energy. Due to the activity of the cells, these defects behave as self-propelled particles and pairwise annihilate until all displacements freeze as cell crowding increases. When confined in mesoscopic circular domains, the system evolves towards two identical +1/2 disclinations facing each other. The most likely reduced positions of these defects are independent of the size of the disk,the cells’ activity or even the cell type, but are well described by equilibrium liquid crystal theory. These cell-based systems thus operate in a regime more stable than other active nematics, which may be necessary for their biological function.

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Year of publication 2016

Laura Wagstaff, Maja Goschorska, Kasia Kozyrska, Guillaume Duclos, Iwo Kucinski, Anatole Chessel, Lea Hampton-O'Neil, Charles R Bradshaw, George E Allen, Emma L Rawlins, Pascal Silberzan, Rafael E Carazo Salas, Eugenia Piddini (2016 Apr 26)

Mechanical cell competition kills cells via induction of lethal p53 levels.

Nature communications : 11373 : DOI : 10.1038/ncomms11373 Learn more
Summary

Cell competition is a quality control mechanism that eliminates unfit cells. How cells compete is poorly understood, but it is generally accepted that molecular exchange between cells signals elimination of unfit cells. Here we report an orthogonal mechanism of cell competition, whereby cells compete through mechanical insults. We show that MDCK cells silenced for the polarity gene scribble (scrib(KD)) are hypersensitive to compaction, that interaction with wild-type cells causes their compaction and that crowding is sufficient for scrib(KD) cell elimination. Importantly, we show that elevation of the tumour suppressor p53 is necessary and sufficient for crowding hypersensitivity. Compaction, via activation of Rho-associated kinase (ROCK) and the stress kinase p38, leads to further p53 elevation, causing cell death. Thus, in addition to molecules, cells use mechanical means to compete. Given the involvement of p53, compaction hypersensitivity may be widespread among damaged cells and offers an additional route to eliminate unfit cells.

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Casimir Emako, Charlène Gayrard, Axel Buguin, Luís Neves de Almeida, Nicolas Vauchelet (2016 Apr 13)

Traveling Pulses for a Two-Species Chemotaxis Model.

PLoS computational biology : e1004843 : DOI : 10.1371/journal.pcbi.1004843 Learn more
Summary

Mathematical models have been widely used to describe the collective movement of bacteria by chemotaxis. In particular, bacterial concentration waves traveling in a narrow channel have been experimentally observed and can be precisely described thanks to a mathematical model at the macroscopic scale. Such model was derived in [1] using a kinetic model based on an accurate description of the mesoscopic run-and-tumble process. We extend this approach to study the behavior of the interaction between two populations of E. Coli. Separately, each population travels with its own speed in the channel. When put together, a synchronization of the speed of the traveling pulses can be observed. We show that this synchronization depends on the fraction of the fast population. Our approach is based on mathematical analysis of a macroscopic model of partial differential equations. Numerical simulations in comparison with experimental observations show qualitative agreement.

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