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Heterogeneous tissues under flow

How do cellular heterogeneity and tissue mechanics shape one another?

Tissues are rarely made of identical cells, in an embryo as in a growing tumour, and what happens to them depends on how a mixed tissue deforms and flows. Does a tissue made of two populations behave as the average of its constituents? And can imposed flows drive the segregation or the mixing of those populations?

The question also comes out of my current work. In the zebrafish embryo, my ferrofluid droplets find more residual stress at the boundary between the eye and the olfactory placode than inside either tissue, and there the loading reshapes them durably. A boundary between two cell populations is where heterogeneity and mechanics meet; this project studies such boundaries in vitro, where the populations and the forces applied to them can be chosen.

Reading mechanics without assuming a constitutive law

The analysis is deliberately model-agnostic: it extracts rheological information from the images before any constitutive law is chosen.

  • Force inference. Relative junction tensions are read from the angles at which cell edges meet, with the tools I developed during my PhD. Their distribution quantifies the heterogeneity of tensions at a given instant.
  • Deformation versus rearrangements. The deformation of the tissue is split into cell-shape changes and neighbour exchanges, as is done for liquid foams and, at the Laboratoire Jean Perrin, for adhesive biomimetic emulsions. The irreversible part carried by rearrangements is a rheological measurement in its own right.
  • Active versus passive. The stochastic-thermodynamics framework of J. O'Byrne separates the part of a dynamics that relaxes towards equilibrium from the part that breaks time-reversal symmetry: what, in the flow of a tissue, is irreducibly active.
Network of cell junctions in an epithelial monolayer, each junction coloured by its inferred tension, from dark red for low to white for high
Force inference on an MDCK monolayer: each junction is coloured by its tension relative to the mean, from dark red (low) to white (high). From my PhD thesis (2019).

Three questions

  1. When an epithelium flows, how much of the flow comes from cells deforming, how much from cells exchanging neighbours, and how much is irreducibly active?
  2. When two cell populations with different adhesion are mixed, is the rheology of the mix the average of its constituents?
  3. Do the relations found in two dimensions hold in three, where ferrofluid droplets can measure the rheology locally?

The project builds on the rest of my work: force inference comes from my thesis on epithelial shape, the ferrofluid droplets from my work on stresses in embryos.

Collaborations