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DE
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Physical approaches to cell dynamics and tissue morphogenesis

We aim to understand the physical principles that underpin the morphogenesis of animals. To do so, we develop and apply quantitative approaches to observe, perturb and predict morphogenetic movements.

Our work addresses fundamental questions in the morphogenesis of multicellular systems: how do cells generate, transmit and respond to mechanical forces, from the supramolecular to the multicellular scale? How are these forces coupled to cell signaling and differentiation processes?  How do organized and functional structures emerge from such interactions? To  address  these questions, we focus on three aspects of morphogenesis:

(1) The organization and supramolecular dynamics of cell contacts;

(2) The mechanics of cell contacts and their remodeling;

(3) The mechanochemical state changes in multicellular self-organization.

We develop both experimental and theoretical approaches to study several in vivo and in vitro multicellular systems : the Drosophila and C. elegans embryos, and mouse embryonic organoids. The originality of our approach lies in the integration of both physics (imaging/mechanics/modeling) and experimental biology to study tissue morphogenesis quantitatively.

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Fluorescence microscopy of a C. elegans embryo: membranes in cyan and histone in orange

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Alumni

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Hashmi Ali
University of Helsinki, postdoctoral fellow
Rulquin Charlotte
Marseille, high school professor
Kong Weiyuan
University of Paris, postdoctoral fellow
Monika Ludanyi
Veracyte, Inc., Product Development Team Leader
Girish Kale, Heidelberg
Postdoctoral fellow
Anaïs Baille, Dresden
Postdoctoral fellow
Eunice Chan
Aix Marseille University, engineer
Olivier Loison
BearingPoint, Paris, data scientist
Pierre Mangeol
Aix Marseille University, lecturer
Rémy Flores Flores
Toulouse, I2MC, Imaging facility leader
Olga Markova
Polytechnique LadHyX, postdoctoral fellow
Binh An Truongquang
Totalenergies Paris, lead data scientist
Jérémie Capoulade
System Engineer, European Space Agency, Netherlands
Matteo Rauzi
University of Nice, France, group leader

Funding bodies

They support our research
ARN
CENTURI
Fondation Recherche Medicale

ERC Synergy 2022 "Breakdance"

Gallery

fluorescence microscopy of a C. elegans embryo (membrane in magenta and Fizzled in cyan)
fluorescence microscopy of a C. elegans embryo (membrane in cyan and DNA in orange)
drosophila wing, spinning disk, 10X
illumination part of a home-made microscope
zoom on a part of the illumination setup of the lattice light sheet microscope

Physical approaches to cell dynamics and tissue morphogenesis

Mechanics of cell contacts and their remodelling

During tissue formation, cell contacts are remodelled by changes in adhesion forces and cell contractility (Lecuit and Lenne, Nature Rev Mol Cell Bio, 2007). To identify the nature of these forces and the mechanical properties of the contacts, we develop and apply physical methods such as laser nanodissection and optical tweezers micromanipulation (Bambardekar et al, PNAS 2015), which are now becoming widespread in the community. Quantification of cell shape changes induced by laser micromanipulation provides direct measurements of the forces acting at cell contacts, and reveals the viscoelastic properties of the tissue (Clément et al, Current Bio 2017). We have shown, using these methods, the distribution of forces (dependent on the molecular motor Myosin-II) that remodel cell contacts during epithelial morphogenesis (Rauzi, Nature Cell Bio 2008). We have shown the importance of geometry in the application of forces shaping cell contacts (Kale et al, Nature Comm 2018). We have highlighted the central role of viscous dissipation in cell and tissue shape changes (Clément et al, Current Bio 2017). The methods developed in our team, coupled with genetic perturbation and mechanical modeling, also reveal how adhesion molecules quantitatively control cell shapes by coupling to contractile forces (Chan, Shivakumar, eLife 2017).
With these approaches, we continue exploring several aspects of cell contact mechanics including the dynamic interplay of adhesion, biochemical signaling, and actomyosin contractility shapes cell contacts using Drosophila and C. elegans embryos as model systems.

Mechanochemical state changes in multicellular self-organization

The formation of multicellular organisms is based on symmetry breaking and tissue patterning events. Among these, the process of gastrulation transforms an apparently homogeneous group of cells into the outline of an organism with recognisable body axes and tissue layers. Our aim is to understand the organizational principles underlying the process of gastrulation in mammals, using an in vitro system composed of embryonic stem cells, called gastruloid. We have recently shown how differentiation, coupled with a change in the mechanical behavior of cells, generates large-scale flow, which in turn polarizes the multicellular system and defines distinct germ layers (Hashmi et al, eLife 2022). This mechanism is reminiscent of the process that occurs at the primitive streak in the embryo and has the characteristics of a mechanochemical phase transition (Lenne and Trivedi, Nature Comm 2022).

New approaches to tissue morphogenesis

Our team has developed and applied over the years several approaches to study cell dynamics and tissue morphogenesis. Such approaches include mechanical measurements and imaging methods. To probe the mechanics of cells in tissues, we introduced optical tweezers for direct manipulation of cell contacts (Bambardekar, PNAS 2015; Chardès et al, JOVE 2018). We have validated and implemented force inference methods in epithelia from cell and tissue scale (Kong et al, 2019, Code available here). We strive to implement long-term imaging methods, including light sheet and non-linear microscopy,  to image the multicellular choreography and the changes of biochemical states leading to the formation of tissues and organs.