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Spatio-Temporal and Mechanical Control of Motile Structures

Team Leader : Gregory Giannone

Grégory Giannone explores the spatiotemporal and mechanical mechanisms driving the dynamics of structures and proteins regulating cell motility

General objective

Cells have the ability to adjust their adhesive and cytoskeletal organizations according to changes in the biochemical and physical nature of their surroundings. In return, by adhering and generating forces on neighboring cells and extracellular matrices cells control their environment, shape and movement. This is true from integrin-based adhesive structures of migrating cells to synapses of neurons. Those adhesive structures are the converging zones integrating biochemical and biomechanical signals arising from the extracellular space and the actin cytoskeleton. Thus, the life-cycle of adhesive and cytoskeletal structures are involved in critical cellular functions such as migration, proliferation and differentiation, and regulate cell behavior in many physiological responses such as development. Alterations of adhesive and cytoskeletal organizations contribute to pathologies including cancer, but also cognitive disorders.

At the molecular, sub-cellular, and cellular levels, cell shaping and motility proceed through cycles lasting from seconds to minutes. During those cycles, critical proteins undergo stochastic motions and transient interactions that are essential to their functions. Regulation of these interactions by forces is at the base of mechano-transduction events controlling cell behavior. Therefore, to understand the molecular mechanisms controlling the life cycle of motile structures, it is crucial to study the position and dynamics of proteins but also their interactions and how mechanical forces control these molecular events.

Our goal is to decipher at the molecular level the spatiotemporal and mechanical mechanisms which control the architecture and dynamics of motile structures including integrin-based AS, the lamellipodium and dendritic spines. Exploration of these new dimensions requires an innovative and multidisciplinary approach combining cell biology, biophysics, biomechanics and advanced optical microscopy techniques including super-resolution microscopy, single protein tracking and quantitative image analysis.

We are developing three specific axes: 1/ Integrin adhesion 2/ Actin in dendritic spines 3/ Super-resolution developments

Research Projects

Integrin adhesion

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Actin in dendritic spines

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Super-resolution developments

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Expertise

  • Single protein tracking sptPALM
  • Super-resolution dSTORM, DNA-PAINT
  • Biophysical tools: Cell stretching
  • News

    Deciphering mechano-biology using super-resolution microscopy

    Cell stretching is amplified by active actin remodeling to deform and recruit proteins in mechano-sensitive structures Detection and conversion of mechanical forces into biochemical signals control cell functions during physiological and pathological processes. Mechano-sensing is based on protein deformations and reorganizations, yet the molecular mechanisms are still unclear. Using a cell stretching device compatible with super-resolution microscopy (SRM) and single protein tracking (SPT), we explored the nanoscale deformations and reorganizations of individual proteins inside mechano-sensitive structures. We achieved SRM after live stretching on intermediate filaments, microtubules and integrin adhesions. Simultaneous SPT and stretching showed that while integrins follow the elastic deformation of the substrate, actin filaments and talin also displayed lagged and transient inelastic responses associated with active acto-myosin remodeling and talin deformations. Capturing acute reorganizations of single-molecule during stretching showed that force-dependent vinculin recruitment is delayed and depends on the maturation of integrin adhesions. Thus, cells respond to external forces by amplifying transiently and locally cytoskeleton displacements enabling protein deformation and recruitment in mechano-sensitive structures.

    Authors: Sophie Massou*, Filipe Nunes Vicente*, Franziska Wetzel*, Amine Mehidi, Dan Strehle, Cecile Leduc, Raphaël Voituriez, Olivier Rossier, Pierre, Nassoy and Gregory Giannone
    * First co-authors

    - Nature Cell Biology, DOI 10.1038/s41556-020-0548-2.
    - Contacts IINS: Grégory Giannone and Filipe Nunes Vicente

    + Cf. INSB website (French) here
    + Cf. Bordeaux Neurocampus website here

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    Selected Publications

  • Sophie Massou, Filipe Nunes Vicente, Franziska Wetzel, Amine Mehidi, Dan Strehle, Cecile Leduc, Raphaël Voituriez, Olivier Rossier, Pierre Nassoy, Grégory Giannone
  • Cell stretching is amplified by active actin remodelling to deform and recruit proteins in mechanosensitive structures Nature Cell Biology (2020)
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  • A. Mehidi, O. Rossier, M. Schaks, A. Chazeau, F. Biname, A. Remorino, M. Coppey, Z. Karatas, J.B. Sibarita, K. Rottner, V. Moreau, G. Giannone
  • Transient Activations of Rac1 at the Lamellipodium Tip Trigger Membrane Protrusion Current Biology (2019)
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  • Paszek M.J., Dufort C.C., Rossier O., Bainer R., Mouw J.K., Godula K., Hudak J.E., Lakins J.N., Wijekoon A., Cassereau L., Rubashkin M.G., Magbanua M.J., Thorn K.S., Davidson M.W., Rugo H.S., Park J.W., Hammer D.A, Giannone G., Bertozzi C.R, Weaver V.M.
  • The cancer cell glycocalyx mechanically primes integrin-dependent growth and survival Nature (2014)
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  • Chazeau A., Mehidi A., Nair D., Gautier J., Leduc C., Chamma I., Kage F., Kechkar A., Thoumine O., Rottner K., Choquet D., Gautreau A., Sibarita J.B., Giannone G.
  • Nanoscale segregation of actin nucleation and elongation factors determines dendritic spine protrusion. EMBO Journal (2014)
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  • Rossier O., Octeau V., Sibarita J.B., Leduc C., Tessier B., Nair D., Gatterdam V., Destaing O., Albiges-Rizo C., Tampé R., Cognet L, Choquet D., Lounis B., and Giannone G.
  • Integrins β1 and β3 exhibit distinct dynamic nanoscale organizations inside focal adhesions. Nature Cell Biology (2012)
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  • Giannone, G., Hosy, E., Levet, F., Constals, A., Schulze, K., Sobolevsky, A. I., Rosconi, M. P., Gouaux, E., Tampé, R., Choquet, D. and Cognet, L.
  • Dynamic super-resolution imaging of endogenous proteins on living cells at ultra-high density. Biophysical Journal (2010)
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    Members

    « Researcher »

    GIANNONE Gregory Researcher gregory.giannone@u-bordeaux.fr +33533514708
    ROSSIER Olivier Researcher olivier.rossier@u-bordeaux.fr +33533514742

    « Technical Staff »

    FABRE Mélanie Technical staff melanie.fabre@u-bordeaux.fr +33533514742

    « Postdoc »

    CHEN Tianchi Postdoc tianchi.chen@u-bordeaux.fr +33533514783
    JOSE Ani Postdoc ani-augustine.jose@u-bordeaux.fr +33533514783

    « PhD student »

    CERCY Maureen PhD student maureen.cercy@u-bordeaux.fr +33533514783
    JOLY Adrien PhD student adrien.joly@u-bordeaux.fr +33533514783
    NUNES VICENTE Filipe PhD student jose-filipe.nunes-vicente@u-bordeaux.fr +33533514783
    ZHOU XUESI PhD student xuesi.zhou@u-bordeaux.fr +33533514783