Edouard Hannezo
@ehannezo.bsky.social
Professor of Biophysics -
@ISTAustria Using physics to understand biological questions, such as how embryos grow!
@ISTAustria Using physics to understand biological questions, such as how embryos grow!
This means that interfaces roughen MUCH faster in disordered environments. And because we find evidence for a critical value of local curvature (tips of tissue "fingers") allowing for detachments, this occurs is disordered environments, but is never reached in free space! (8/n)
May 26, 2025 at 8:32 AM
This means that interfaces roughen MUCH faster in disordered environments. And because we find evidence for a critical value of local curvature (tips of tissue "fingers") allowing for detachments, this occurs is disordered environments, but is never reached in free space! (8/n)
Turns out we can map invasion in different environments to different universality classes of interface roughening processes (KPZ vs quenched KPZ) - which predicts very well both exp. and simulation dynamics (7/n)
May 26, 2025 at 8:32 AM
Turns out we can map invasion in different environments to different universality classes of interface roughening processes (KPZ vs quenched KPZ) - which predicts very well both exp. and simulation dynamics (7/n)
Long story-short: it's actually not so much local pore geometries driving detachments, but rather a more global effect of temporal integration! The collective cell interfaces gradually roughens over time - and detachments occurs at a critical value of interfacial roughness! (6/n)
May 26, 2025 at 8:32 AM
Long story-short: it's actually not so much local pore geometries driving detachments, but rather a more global effect of temporal integration! The collective cell interfaces gradually roughens over time - and detachments occurs at a critical value of interfacial roughness! (6/n)
So we turned to minimal active particle simulations, and found that this effect of detachments/single cell invasion in disordered environment was a highly robust feature - enabling us to use simulations to do hypothesis-testing! (5/n)
May 26, 2025 at 8:32 AM
So we turned to minimal active particle simulations, and found that this effect of detachments/single cell invasion in disordered environment was a highly robust feature - enabling us to use simulations to do hypothesis-testing! (5/n)
Most of our initial guesses turned out to be wrong! It’s not the challenge due to small pores in disordered environments (no detachments still with small ordered pores), nor simply due to a funnel/traffic jam effect of pore size gradients (no detachments in graded regular environments) (4/n)
May 26, 2025 at 8:32 AM
Most of our initial guesses turned out to be wrong! It’s not the challenge due to small pores in disordered environments (no detachments still with small ordered pores), nor simply due to a funnel/traffic jam effect of pore size gradients (no detachments in graded regular environments) (4/n)
Surprisingly, the density of obstacles per se mattered less than the disorder/heterogeneity in their positioning! Cancer cells invaded as a collective in free space+ordered environment, but as single cells in disordered environments! (3/n)
May 26, 2025 at 8:32 AM
Surprisingly, the density of obstacles per se mattered less than the disorder/heterogeneity in their positioning! Cancer cells invaded as a collective in free space+ordered environment, but as single cells in disordered environments! (3/n)
Excited about the new work from Z. Dunajova & S. Tasciyan (with the Sixt lab @ISTA) - how the mechanical heterogeneity of the environment can be (by itself!) a driver of tumor cell dissemination! www.biorxiv.org/content/10.1... Combination of in vitro exp, simulations and KPZ stat phys!👇🧵1/n
May 26, 2025 at 8:32 AM
Excited about the new work from Z. Dunajova & S. Tasciyan (with the Sixt lab @ISTA) - how the mechanical heterogeneity of the environment can be (by itself!) a driver of tumor cell dissemination! www.biorxiv.org/content/10.1... Combination of in vitro exp, simulations and KPZ stat phys!👇🧵1/n
Altogether, we can then fully parametrize a phase diagram of organoid morphogenesis, showing how mechanosensation drives bistability, and thus robustness against mechanical perturbation once morphogenesis is complete! 9/n
March 10, 2025 at 11:49 AM
Altogether, we can then fully parametrize a phase diagram of organoid morphogenesis, showing how mechanosensation drives bistability, and thus robustness against mechanical perturbation once morphogenesis is complete! 9/n
We also performed a series of reversible pharmacological perturbations to test the model! Inhibition of contractility + volume increase reverses crypt morphogenesis... and crypts cannot bud again even when contractility inhibition is lifted (at high lumen volume) 7/n
March 10, 2025 at 11:49 AM
We also performed a series of reversible pharmacological perturbations to test the model! Inhibition of contractility + volume increase reverses crypt morphogenesis... and crypts cannot bud again even when contractility inhibition is lifted (at high lumen volume) 7/n
Inflation experiments + live-imaging of myosin localization confirm the hypothesis where changes in crypt curvature cause a loss of apical actomyosin... demonstrates a positive feedback loop from curvature to contractility leading to bistability! 6/n
March 10, 2025 at 11:49 AM
Inflation experiments + live-imaging of myosin localization confirm the hypothesis where changes in crypt curvature cause a loss of apical actomyosin... demonstrates a positive feedback loop from curvature to contractility leading to bistability! 6/n
This was hard to get in a purely mechanical model - but considering mechano-sensing generically gives rise to large bistability regions! We thus hypothesized that lumen volume changes have both a purely passive/mechanical effect, but are also actively sensed in crypts! 5/n
March 10, 2025 at 11:49 AM
This was hard to get in a purely mechanical model - but considering mechano-sensing generically gives rise to large bistability regions! We thus hypothesized that lumen volume changes have both a purely passive/mechanical effect, but are also actively sensed in crypts! 5/n
In physics, this is reminiscent of hysteresis, i.e. when past history of perturbations dictates the state of a system - and occurs for instance in bistable systems with several mechanically stable states! Indeed, plotting morphology against volume reveals two stable branches 4/n
March 10, 2025 at 11:49 AM
In physics, this is reminiscent of hysteresis, i.e. when past history of perturbations dictates the state of a system - and occurs for instance in bistable systems with several mechanically stable states! Indeed, plotting morphology against volume reveals two stable branches 4/n
Previously, we had shown that crypt morphogenesis in organoids comes both from actomyosin apical constriction in stem cells, and osmotic forces/volume changes from villus cells (Yang, Xue, NCB, 2021) - but how are these events coordinated? is it robust? (2/n)
March 10, 2025 at 11:49 AM
Previously, we had shown that crypt morphogenesis in organoids comes both from actomyosin apical constriction in stem cells, and osmotic forces/volume changes from villus cells (Yang, Xue, NCB, 2021) - but how are these events coordinated? is it robust? (2/n)
Fun group retreat in the Austrian alps with @priscaliberali.bsky.social! And perfect time to celebrate our new joint paper (from Shi-Lei Xue & Qiutan Yang) out on how mechanochemical bistability confers robustness to intestinal organoids! www.nature.com/articles/s41... - see 🧵! (1/n)
March 10, 2025 at 11:49 AM
Fun group retreat in the Austrian alps with @priscaliberali.bsky.social! And perfect time to celebrate our new joint paper (from Shi-Lei Xue & Qiutan Yang) out on how mechanochemical bistability confers robustness to intestinal organoids! www.nature.com/articles/s41... - see 🧵! (1/n)
We performed oncogenic activation (basal cell carcinoma) and lineage-tracing in mouse epidermis - and measured tumor single cell morphometrics --> prism shapes consistent with enhanced basal adhesion - to a degree consistent with our prediction from previous fate oucomes! 8/n
December 17, 2024 at 2:11 PM
We performed oncogenic activation (basal cell carcinoma) and lineage-tracing in mouse epidermis - and measured tumor single cell morphometrics --> prism shapes consistent with enhanced basal adhesion - to a degree consistent with our prediction from previous fate oucomes! 8/n
Crucially, imbalances in tension/adhesion should also be manifest in single cell morphometrics- meaning we can theoretically derive a master curve linking long-term fate outcomes from static cell morphometrics! Is this true in data? (7/n)
December 17, 2024 at 2:11 PM
Crucially, imbalances in tension/adhesion should also be manifest in single cell morphometrics- meaning we can theoretically derive a master curve linking long-term fate outcomes from static cell morphometrics! Is this true in data? (7/n)
We realized that fate choices are extremely sensitive to imbalance in adhesions/tensions! If tumor cells have slightly higher basal adhesion, this gives their progeny them a slight advantage to stay in the basal layer, which is compounded in time! (6/n)
December 17, 2024 at 2:11 PM
We realized that fate choices are extremely sensitive to imbalance in adhesions/tensions! If tumor cells have slightly higher basal adhesion, this gives their progeny them a slight advantage to stay in the basal layer, which is compounded in time! (6/n)
Although tissue rheology (e.g. liquid or solid) has little impact on average properties such as clone sizes, it was still be traced back to very different patterns of cell and clonal shape - something often discarded in lineage tracing experiments that needs to be reanalyzed! 4/n
December 17, 2024 at 2:11 PM
Although tissue rheology (e.g. liquid or solid) has little impact on average properties such as clone sizes, it was still be traced back to very different patterns of cell and clonal shape - something often discarded in lineage tracing experiments that needs to be reanalyzed! 4/n
Seminal work has shown how single cell fate is affected by different mechanical forces, but how are fate choices collectively balanced in complex multilayered tissues? To model skin, we start with a 3D vertex model with proliferation only in the basal cells (2/n)
December 17, 2024 at 2:11 PM
Seminal work has shown how single cell fate is affected by different mechanical forces, but how are fate choices collectively balanced in complex multilayered tissues? To model skin, we start with a 3D vertex model with proliferation only in the basal cells (2/n)
Happy to share the latest work from Preeti Sahu, with Adriana Sanchez-Danes on the biomechanics of cell fate choices during tumor initiation! We implement/test a 3D vertex model with proliferation and fate choices for multilayered tissues! See 🧵 below (1/n) bit.ly/3ZXxJzk
December 17, 2024 at 2:11 PM
Happy to share the latest work from Preeti Sahu, with Adriana Sanchez-Danes on the biomechanics of cell fate choices during tumor initiation! We implement/test a 3D vertex model with proliferation and fate choices for multilayered tissues! See 🧵 below (1/n) bit.ly/3ZXxJzk
New paper out with the Kicheva group by S. Lehr and D. Bruckner! 🧪 Develops a new 2D neural tube organoid, and models its striking self-organized patterns! Key finding: patterning via 2-phase dynamics of BMP, which acts like a temporal relay balancing sequential fate decisions! bit.ly/3OJti4G
December 6, 2024 at 2:46 PM
New paper out with the Kicheva group by S. Lehr and D. Bruckner! 🧪 Develops a new 2D neural tube organoid, and models its striking self-organized patterns! Key finding: patterning via 2-phase dynamics of BMP, which acts like a temporal relay balancing sequential fate decisions! bit.ly/3OJti4G