Manning Research Group

Manning Research Group

@manningresearch.bsky.social

Manning Research Group at Syracuse University: theory and computation focused on cells, grains, tissues, glasses, and other out-of-equilibrium disordered matter

245 followers67 following165 posts

New work in PNAS, spearheaded by former postdoc Sadjad Arzash in collaboration with Andrea Liu, developing a principled, top-down & bottom up approach for figuring out what algorithms development uses to execute tasks...

Sadjad Arzash@sadjadarzash.bsky.social

1/6 Can learning in physical systems help us understand how embryos shape themselves? Our PNAS paper with Andrea Liu & @manningresearch.bsky.social introduces a tunable-matter framework for morphogenesis, using convergent extension as a case study. www.pnas.org/doi/10.1073/...

Excited about this new paper from our research group on cell division in stratified epithelia, spearheaded by Dr. Somiealo Azote and @dr-rajendra-s-negi.bsky.social. See the great tutorial from Rajendra!

Rajendra Singh Negi@dr-rajendra-s-negi.bsky.social

(1/n) Does basal stem cell division orientation regulate skin stratification and tissue mechanics? And can tissue mechanics feed back to control division orientation? In our new preprint, we use a 3D vertex model to explore this @manningresearch.bsky.social @somiealo.bsky.social

Manning research group represents at the APS March meeting (aka Global Summit)! I am so proud of all the great work that will be presented by current students and postdocs from our research group. Here's a time-ordered list of talks, please check them out if you're in Denver this week!

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Somiealo Azote epse Hassikpezi, A Predictive Model for Coupling Cell Division Orientation to Tissue Mechanics During Epithelial Morphogenesis, March 19th, 8:36–8:48 a.m. | Convention Center, Bluebird 2B Mechanics of Cells and Tissues IV | MAR-S58

Tanya Chhabra, Impact of tunable interactions on emergent behavior in a random field Ising model with feedback, March 19th, 12:48–1:00 p.m. | Convention Center, Bluebird 2A Physics of Learning and Adaptation III | MAR-U57

Manning research group represents at the APS March meeting (aka Global Summit)! I am so proud of all the great work that will be presented by current students and postdocs from our research group. Here's a time-ordered list of talks, please check them out if you're in Denver this week!

View full thread

Manning research group represents at the APS March meeting (aka Global Summit)! I am so proud of all the great work that will be presented by current students and postdocs from our research group. Here's a time-ordered list of talks, please check them out if you're in Denver this week!

View full thread

Rajendra Negi, Mechanobiological Regulation of Symmetry Breaking During Zebrafish Embryogenesis: Interplay of Myosin Activity, Mechanical Forces, and External Flows, March 16th, 5:30–5:42 p.m. | Convention Center, Bluebird 2E Morphogenesis I | MAR-C61

Manning research group represents at the APS March meeting (aka Global Summit)! I am so proud of all the great work that will be presented by current students and postdocs from our research group. Here's a time-ordered list of talks, please check them out if you're in Denver this week!

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Notch activity itself is gated by tissue stiffness and basal layer density/cell shape. This generates an elegant self-organizing feedback loop where delamination is directly link to the abundance and packing of basal layer stem cells, explaining the robustness of epithelial self-renewal.

Future work: A key remaining open question on the physics side is precisely how this tissue-stiffness-dependent Notch activation is triggered – how do only a subset of cells (exactly the right number, perhaps not too close together) decide to commit?

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Cell state commitment in the basal layer activates Notch signaling. At E15.5 and E16.5 a population of Notch positive cells emerges that share characteristics of both basal and suprabasal cells, and also exhibit cell shapes and protein localization patterns consistent with cells that delaminate.

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At E14.5, only small changes to a cell’s mechanics (x-axis) are needed to get a cell to robustly delaminate (fraction of delaminating cells, y-axis -> 1). At E15.5 and E16.5, a very large change to cell mechanics is required to get a cell to delaminate.

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We can use an Arrhenius approximation to extract the magnitude of the mechanical barrier to delamination from the rates of cell delamination. We find a large mechanical barrier emerges at E15.5 (and the barrier is small before that).

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The results are that at earlier stages (E14.5) the basal layer is soft (small delta s) with small heterotypic tension at the apical side (small sigma_a) and a positive, repulsive interaction with the basement membrane (sigma_b).

At later stages (E15.5), the interaction with the basement membrane becomes wetting (negative sigma_b), and the heterotypic apical tension and tissue stiffness both increase, with further tissue stiffening even later at (E16.5).

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Three vertex model parameters control those observables – the cell stiffness parameterized in terms of a cell shape (delta s), a wetting tension with the basement membrane (sigma_b), and a heterotypic interfacial tension at the apical side of basal cells interacting with suprabasal cells (sigma_a).

We used another set of data collapses to predict how each observable depends on model parameters, allowing us to use an overconstrained solver to determine the vertex model parameter that best match our experimental observations!

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In both simulations and experiments, we can measure 4 quantities – apical angle of basal cells, orientation of later interfaces with respect to the basement membrane, overall roughness of the basal-suprabasal interface, and height of basal cells.

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A vertex model simulation data collapse demonstrates that the rate at which cells are able to move upwards depends on a precise combination of the apical and basal tensions of the committed cell, as well as on the stiffness of surrounding cells.

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We demonstrate that there is a switch in multilayering strategy across development. At earlier stages, the mechanical barrier is quite small, so cells can easily divide perpendicularly to the basement membrane to populate upper layers.

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Such feedbacks are becoming better understood in the small intestine, where stem cells reside in a “closed niche” defined by the crypt, but the stratified epidermis is an “open niche” that lack obvious morphological and geometric cues and even distinct molecular markers of cell states.

Here, we study the developing stratified mouse epidermis to show that the physical separation of basal stem cells from suprabasal differentiating cells is driven by a mechanical boundary that forms between the layers during development.

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