Rikki Garner
rikkigarner.bsky.social
Rikki Garner
@rikkigarner.bsky.social
Helen Hay Whitney Fellow with Sean Megason at HMS SysBio (PhD w/ Julie Theriot). Biophysicist and quantitative cell biologist, integrating theory and experiment.
Thanks for sharing! Zebrafish is such a perfect model system to study tissue fluidity. Here's a sneak peak of what I'm working on now!
April 25, 2025 at 11:47 AM
And we are really excited to think about how these principles can be used to understand how patterns are formed in development, lost in diseases such as cancer, regained in wound healing and regeneration, and can be engineered in synthetic organoid and embryoid systems. 18/20
April 24, 2025 at 1:19 PM
Overall, our work shows that tissues can readily tune their fluidity in order to freeze, catalyze, or erase multicellular patterns! 17/20
April 24, 2025 at 1:19 PM
Intriguingly, even though we only altered the adhesion strength, cells appeared to naturally increase their motility proportionally with cell-cell adhesion, in order to maintain a permissive fluidity for sorting. 16/20
April 24, 2025 at 1:19 PM
To interrogate the consequences of this constraint on tissue fluidity experimentally, we varied adhesion protein expression levels in the cell sorting assay, and fit them to simulations to infer the energies of migration and adhesion across experimental conditions. 15/20
April 24, 2025 at 1:19 PM
So overall, we find that cell sorting sits directly between a “rock” where cells essentially can’t move, and a “hot place” where entropy and random mixing dominates – such that tissue fluidity must be precisely controlled in order for sorting to occur. 14/20
April 24, 2025 at 1:19 PM
And when I say sorting is too slow to occur on biological timescales, I’m not kidding! Below a certain tissue fluidity, cells are effectively frozen in place for eternity. This is due to the glassy nature of tissues. 13/20
April 24, 2025 at 1:19 PM
Playing back some example simulations, you can immediately see why tissue fluidity matters. If fluidity is too low, cells can’t sort because they can’t move. But if tissue fluidity is too high, cells mix randomly. In most cases, an intermediate tissue fluidity is optimal for sorting. 11/20
April 24, 2025 at 1:19 PM
So, how does tissue fluidity impact cell sorting? We found that no matter how we changed tissue fluidity in the model, we saw substantial changes in the rate or accuracy of sorting (or both!). Here’s what the pattern looks like after 2 days of sorting for each condition. 10/20
April 24, 2025 at 1:19 PM
In fact, because it fits so well, we can estimate the energies of cell motility and cell-cell adhesion in any experimental cell sorting assay by fitting the sorting dynamics to our model. More on this later… 9/20
April 24, 2025 at 1:19 PM
To determine the predictive power of our model, @seanemcgeary.bsky.social mixed fibroblasts cells expressing different cadherins, and used quantitative imaging to watch them sort. We were excited to see that the model recapitulated the experiments in striking detail! 8/20
April 24, 2025 at 1:19 PM
The model is based on a powerful tool in physics called the Ising model. Here’s an example. On top, each cell is colored by a unique ID, so you can visualize cell mixing. On the bottom, cells are colored by their cell type, so you can watch them sort. Beautiful, right? 7/20
April 24, 2025 at 1:19 PM
So how does tissue fluidity affect the ability of cells to build patterns? To answer this question, we built a model incorporating both tissue fluidity and cell sorting. As cells move around (based on the tissue fluidity), they group together with cells of the same cell type. 6/20
April 24, 2025 at 1:19 PM
As they move, cells build breathtakingly beautiful patterns in the embryo – stripes, checkerboards, spheres, tubes… Here are just a few of my favorite examples. Like the members of a marching band, cells rearrange into formations to build the embryo. 5/20
April 24, 2025 at 1:19 PM
What determines how quickly cells can move through a tissue in the first place? A lot of things! But, to make things simple, we often sum it up as “tissue fluidity”. It’s an analogy: cells in a tissue act like molecules in a fluid… 2/20
April 24, 2025 at 1:19 PM
In developing embryos, cells move a lot! Plenty of that movement is random. Is random cell mixing a feature or bug for tissue patterning? Turns out, it’s both! Excited to share the 1st preprint from my postdoc w/ Sean Megason @seanemcgeary.bsky.social and Allon Klein. 1/20 doi.org/10.1101/2025...
April 24, 2025 at 1:19 PM