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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


Actin in dendritic spines


Super-resolution developments



  • 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


    Orré T., Rossier O. and Giannone G. in Nature Communications - May 2021

    Focal adhesions (FAs) initiate chemical and mechanical signals involved in cell polarity, migration, proliferation and differentiation. Super-resolution microscopy revealed that FAs are organized at the nanoscale into functional layers from the lower plasma membrane to the upper actin cytoskeleton. Yet, how FAs proteins are guided into specific nano-layers to promote interaction with given targets is unknown. Using single protein tracking, super-resolution microscopy and functional assays, we link the molecular behavior and 3D nanoscale localization of kindlin with its function in integrin activation inside FAs. We show that immobilization of integrins in FAs depends on interaction with kindlin. Unlike talin, kindlin displays free diffusion along the plasma membrane outside and inside FAs. We demonstrate that the kindlin Pleckstrin Homology domain promotes membrane diffusion and localization to the membrane-proximal integrin nano-layer, necessary for kindlin enrichment and function in FAs. Using kindlin-deficient cells, we show that kindlin membrane localization and diffusion are crucial for integrin activation, cell spreading and FAs formation. Thus, kindlin uses a different route than talin to reach and activate integrins, providing a possible molecular basis for their complementarity during integrin activation.

    Nature Communications - DOI 10.1038/s41467-021-23372-w
    published online: 25 May 2021

    - Contacts IINS: Olivier Rossier and Grégory Giannone


    Selected Publications

  • Thomas Orré, Adrien Joly, Zeynep Karatas, Birgit Kastberger, Clément Cabriel, Ralph T. Böttcher, Sandrine Lévêque-Fort, Jean-Baptiste Sibarita, Reinhard Fässler, Bernhard Wehrle-Haller, Olivier Rossier, Grégory Giannone
  • Molecular motion and tridimensional nanoscale localization of kindlin control integrin activation in focal adhesions Nature Communications (2021)
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  • Mariem Souissi, Julien Pernier, Olivier Rossier, Gregory Giannone, Christophe Le Clainche, Emmanuèle Helfer, Kheya Sengupta
  • Integrin-Functionalised Giant Unilamellar Vesicles via Gel-Assisted Formation: Good Practices and Pitfalls. International journal of molecular sciences (2021)

  • 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)

  • 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)

  • 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)

  • 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)

  • 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)

  • 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)


    « Researcher »

    GIANNONE Gregory Researcher +33533514708
    ROSSIER Olivier Researcher +33533514742

    « Technical Staff »

    FABRE Mélanie Technical staff +33533514742

    « Postdoc »

    CHEN Tianchi Postdoc +33533514783
    JOSE Ani Postdoc +33533514783

    « PhD student »

    CERCY Maureen PhD student +33533514783
    JOLY Adrien PhD student +33533514783
    MILANOVIC Violeta PhD student +33533514700
    ZHOU XUESI PhD student +33533514783