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Starting this New Year with a preprint from great former postdoc @AleMongera and other awesome former and present lab members: "Mechanics of the cellular microenvironment as perceived by cells in vivo". https://www.biorxiv.org/content/10.1101/2021.01.04.425259v1 Here is a short version... 
Our goal here was to identify the mechanical parameters(s) that cells probe in the complex mechanical landscape of a living embryonic tissue, in vivo and in situ, especially as cells undergo differentiation.
We know that cells can sense and transduce mechanical cues from the microenvironment. For instance, varying microenvironment stiffness in vitro has been shown to affect important cell behaviors, including proliferation and differentiation. But...
... what happens in vivo, within developing embryos, as cells differentiate to build embryonic structures? What mechanical parameters do cells perceive? We studied this problem during mesodermal cell specification in zebrafish 
To sense the material properties of any material, it is necessary to mechanically probe it. In complex materials, the perceived mechanical properties depend on the strains and timescales at which the material is probed. And tissues are complex, living materials...
So, we first identified the length scale controlling the onset of tissue plasticity (irreversible deformation), and found that only deformations above a threshold length, namely the length of cell-cell contacts, generate irreversible tissue deformations.
This is what happens in foam-like inert materials. In our case, the tissue plastic deformations are caused by cell rearrangements, and the material yield strain (strain above which there is plastic deformation) is controlled by length of cell-cell contacts.
So, do cells probe tissue mechanics below (viscoelastic) or above (plastic) the yield strain? We measured the strains that cells generate at cell-cell contacts and by the extension of protrusions between cells and found that cells probe the tissue below yield strain
But, since the mechanics of the tissue below yield strain is time-dependent, we also measured the characteristic timescales at which cell junction dynamics and protrusions probe the microenvironment...
... and it turns out cells in the tissue preferentially probe it at timescales of 1-2 minutes (within our detection limits).
So, we measured the tissue mechanics as mesodermal progenitors differentiate for the strain- and time-scales at which cells seem to probe the tissue, and found that the perceived tissue stiffness decreases over time (due to stress relaxation).
Comparing the strains and timescales at which cells probe their microenvironment with the measured strain and time-dependent tissue mechanics indicates that cells preferentially probe the stiffness associated with deformations of the foam-like tissue architecture.
It is unclear if cells sense this stiffness and respond to it, but it seems that this stiffness is the mechanical parameter they probe. Since it is directly linked to tissue architecture, it could be that cells indirectly probe the level of cellular confinement in the tissue.
Indeed, this cell-probed stiffness shows a minimal value in the region of the tissue where mesodermal progenitors differentiate into mesodermal cells. Correlation, but not causation at this point...
Shout out to all the former and present lab members who contributed to this work: @AleMongera, Marie Pochitaloff, Hannah Gustafson, @regagino and Payam Rowghanian. Great team work!
