Biology Inspired Physics at Mesoscales

Team Publications

Year of publication 2016

Laxsoomee Bhoonderowa, Fatima Hameurlaine, Atousa Arbabian, Fahima Faqir, François Amblard, Sylvie Coscoy (2016 Aug 31)

Polycystins and intercellular mechanotransduction: A precise dosage of polycystin 2 is necessary for alpha-actinin reinforcement of junctions upon mechanical stimulation.

Experimental cell research : 348 : 23-35 : DOI : 10.1016/j.yexcr.2016.08.021 Learn more
Summary

Polycystins 1 and 2, which are mutated in Autosomal Polycystic Kidney Disease, are involved in mechanotransduction through various mechanisms. In renal cells, polycystins not only have an important mechanotransductive role in primary cilia but are also present in intercellular contacts but their role there remains unclear. Here, we address the hypothesis that polycystins are involved in mechanotransduction via intercellular junctions, which would be expected to have consequences on tissue organization. We focused on the role of polycystin 2, which could be involved in mechanical organization at junctions either by its channel activity or by the direct recruitment of cytoskeleton components such as the F-actin cross-linker α-actinin. After mechanical stimulation of intercellular junctions in MDCK renal epithelial cells, α-actinin is rapidly recruited but this is inhibited upon overexpression of PC2 or the D509V mutant that lacks channel activity, and is also decreased upon PC2 silencing. This suggests that a precise dosage of PC2 is necessary for an adequate mechanosensitive α-actinin recruitment at junctions. At the multicellular level, a change in PC2 expression was associated with changes in velocity in confluent epithelia and during wound healing together with a loss of orientation. This study suggests that the mechanosensitive regulation of cytoskeleton by polycystins in intercellular contacts may be important in the context of ADPKD.

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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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Year of publication 2015

Simon Garcia, Edouard Hannezo, Jens Elgeti, Jean-François Joanny, Pascal Silberzan, Nir S Gov (2015 Dec 1)

Physics of active jamming during collective cellular motion in a monolayer.

Proceedings of the National Academy of Sciences of the United States of America : 15314-9 : DOI : 10.1073/pnas.1510973112 Learn more
Summary

Although collective cell motion plays an important role, for example during wound healing, embryogenesis, or cancer progression, the fundamental rules governing this motion are still not well understood, in particular at high cell density. We study here the motion of human bronchial epithelial cells within a monolayer, over long times. We observe that, as the monolayer ages, the cells slow down monotonously, while the velocity correlation length first increases as the cells slow down but eventually decreases at the slowest motions. By comparing experiments, analytic model, and detailed particle-based simulations, we shed light on this biological amorphous solidification process, demonstrating that the observed dynamics can be explained as a consequence of the combined maturation and strengthening of cell-cell and cell-substrate adhesions. Surprisingly, the increase of cell surface density due to proliferation is only secondary in this process. This analysis is confirmed with two other cell types. The very general relations between the mean cell velocity and velocity correlation lengths, which apply for aggregates of self-propelled particles, as well as motile cells, can possibly be used to discriminate between various parameter changes in vivo, from noninvasive microscopy data.

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