DS04 - Vie, santé et bien-être

COincidence DEtection in Cellular IDEntity – CODECIDE

Cell anchoring zones to matrix, as receptor trapping site to orchestrate biological responses

Recepteur organization and cell signaling

Correlating the spatiotemporal organization of cell receptors to cell mechanics and differentiation

Extracellular matrix proteins transmit multiple signals to cells in a temporally regulated and spatially structured manner. Thus, fibronectin, allows binding to integrin adhesive receptors and to growth factors. The proximity of these interaction sites allows a functional juxtaposition between integrins and growth factor receptors. Our previous work showed the ability of the growth factor Bone Morphogenetic Protein 2 (BMP2) presented by a soft matrix was sufficient to induce cell spreading. This spreading is associated with the formation of adhesion structures (focal adhesion, FA) that depend on integrin receptors. However, the mechanisms and temporal events allowing concerted responses between integrin receptors and growth factor receptors remained unexplored. The system is further complicated by the fact that there are several receptors that can respond to the BMP2 signal.

Dynamic and high-resolution imaging, optogenetics and biomaterials show that the spatial organization of growth factor receptor subunits on the cell surface is a response to physical and biochemical signals from the extracellular matrix.

The activity of BMPs on cell differentiation depends on the stiffness of the environment while inducing spatial organization of BMP2 receptor subunits. Matrix adhesion sites are trapping sites for some BMP receptor subunits. This segregation on either side of the adhesion sites is mechanically controlled and allows the formation of different complexes to coordinate adhesion and differentiation processes.

The spatio-temporal organization of BMP receptors opens new avenues to understand the functional dualities (oncogenic versus tumor suppressor) between BMP receptor subunits.

These results have been disseminated in journals in different disciplines showing the importance of interdisciplinarity in the advancement of research work but also the filing of a patent for the development of automated methods. Thus, our fundamental program has brought together cell biologists, biomaterials engineers and biophysicists allowing scientific and technological advances. The CODECIDE project coordinated by Corinne Albiges-Rizo and associating Catherine Picart and Benoit Ladoux started in 2018 for a duration of 4 years benefiting from an ANR grant of 613 k€ for a global cost of 2873 k€.

Regenerative medicine is predicated on understanding the molecular basis of tissue-specific differentiation and then applying the appropriate soluble and physical cues to drive stem cell fate. Our previous results have suggested that cells can encode physical and biochemical information from extracellular matrix by detecting the occurrence of temporally close but spatially-distributed signals, such as BMP-2 and Fibronectin. We hypothesize that the distribution of adhesive and growth factor inputs and their detection coincidence would be the basis of BMP receptor/integrin cooperation to specify cell fate and identity. Based on a multidisciplinary network, the CODECIDE project will i) design biomaterials and develop optogenetics approach to spatio-temporally control receptor proximity, ii) establish correlation between spatio-temporal receptor patterning and cell mechanics and iii) investigate cell fate under spatiotemporally controlled patterning in order to predict new biomaterials engineered to elicit targeted cellular responses in regenerative medicine. This research program will provide novel spatio-temporal insights to drive the continuum from the cell membrane to the nucleus where the transcription factors are translocated to active gene and specify cell identity.

Project coordination

Corinne ALBIGES-RIZO (Institute for Advanced Biosciences (IAB) - CR UGA / Inserm U1209 /CNRS UMR5309)

The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.


IAB - Institute for Advanced Biosciences Institute for Advanced Biosciences (IAB) - CR UGA / Inserm U1209 /CNRS UMR5309
BRM - Biomimetism and Regenerative Medicine BRM - Biomimetism and Regenerative Medicine
IJM - Institut Jacques Monod IJM - Institut Jacques Monod

Help of the ANR 521,605 euros
Beginning and duration of the scientific project: December 2017 - 48 Months

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