The poro-active nature of biological tissues participates to the active coupling of mechanical and biochemical cues. Such coupling can ultimately convey distant signals and determine cell and tissue fate.
This hypothesis is supported by the observation that the mechanical state of the extracellular matrix selectively influences the transport of molecules within it. On the one hand, we previously observed that the diffusion of macromolecules through the extracellular matrix depends on their size. On the other hand, we measured that the diffusion of a tracer (SRB) through a hydrogel increases monotonously with the compressional state of the gel. However, it is reported that large particles can be transported through the extracellular matrix (ECM) of fibrous tissue, in an apparent contradiction between the small mesh size of the ECM and the large size of the particles.
The focus of this internship is to determine how a pulsatile mechanical stress influences the hydrodynamic transport of biochemical molecules through a synthetic hydrogel or through a reconstituted extracellular matrix. The student will first develop a microfabricated device, allowing him to mechanically stress the hydrogel. Then, he will measure how the applied stresses and deformations induce solute or particle fluxes in the gel.
Then, he will characterize how the porosity and tortuosity are altered under stress, when the hydrogel is doped with uncompressible inclusions that mimic the presence of cells.
The internship candidate will strongly interact with our collaborators at the Laboratory 3SR (Mehdi Bouzid).
References
Optical sensing of mechanical pressure based on diffusion measurement in PAA cell-like barometers; F. Ingremeau, M. E. Dolega, J. Gallagher, I. Wang, G. Cappello, A. Delon; Soft Matter, (2017) 13: 4210
Extracellular matrix in multicellular aggregates acts as a pressure sensor controlling cell proliferation and motility; M. Dolega, S. Monnier, B. Brunel, J.-F. Joanny, P. Recho, G. Cappello*; eLife (2021) 10: e63258
S. Lenzini, R. Bargi, G. Chung, and J.-W. Shin. “Matrix mechanics and water permeation regulate extracellular vesicle transport”. In: Nat.Nanotechnol. 15 (2020), pp. 217–223. doi: 10.1038/s41565-020-0636-2.
G. van Niel, D. R. F. Carter, A. Clayton, D. W. Lambert, G. Raposo, and P. Vader. “Challenges and directions in studying cell–cell communication by extracellular vesicles”. In: Nat Rev Mol Cell Biol 23 (2022), pp. 369–382. doi: 10.1038/s41580-022-00460-3.
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