epithelial mechanics fan club

I just started a cell biology and biophysics group at EPFL, Switzerland that will investigate how cells endure mechanical stress and release large cytoplasts.

Get in touch if you’d like to join!
See more at celldynamicslab.com

Flipper-TR help introduce membrane mechanics to measurable cell biology experiments. Its future lies in combining composition, mechanics, and protein interactions, and interpreting it with care.

Contact me if you need help, advice, or discussion!
Thanks to @epimechfc.bsky.social for this platform💙

📄 Finally, the success of the probe comes in part from its availability. The University of Geneva licensed the probe to @spirochrome.com @lreymond.bsky.social which made it available around the world, along with new versions like Halo-Flippers

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📄 MANY cool applications for the probe are on the way or have been published... as in mitochrondrial fission
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from @sulianamanley.bsky.social or to assess peptide interaction to in vitro lipid bilayers
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from @javierespadas.bsky.social

📄 A major effort is carried out by the community to benchmark Flipper-TR alongside other membrane probes. This elegant paper from @sciezgin.bsky.social quantified the FLIM response of several probes in parallel

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📄 Methods: A practical FLIM analysis-focused guide: acquisition, fitting strategies, phasors, and interpretation. It clearly explains how lifetime reflects lipid packing, and where over-interpretation of “tension” can go wrong.

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📄 Methods: Experimental best practices covering labelling, imaging, and controls across systems. Essential reading to avoid technical artifacts and misleading comparisons.

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📄 Tension gradients during migration. Using Flipper-TR FLIM, we showed that membrane tension gradients exist in all adherent cells and are actively maintained by actin and adhesion, not passively equilibrating. @rouxlab.bsky.social and Aumeier lab

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📄 In cells, osmotic shocks shift Flipper-TR lifetime consistently with increased or decreased membrane tension, provided composition is controlled. This paper also compared quantitatively tether force and F-TR lifetime measurements @chloeroffay.bsky.social

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💡 By tuning lipid composition and applied tension in GUVs, Flipper-TR lifetime could be quantitatively related to membrane mechanical state, establishing the physical basis for cellular measurements made later.

📄 The first study from @rouxlab.bsky.social in cells showed that planarizable Flipper probes report lipid composition, packing and phase state in GUVs, and respond to tension via changes in lipid order, both in model membranes and cells. @colomlab.bsky.social

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💡 Core principle:
Flipper-TR reports changes in the lipid packing / lateral pressure of the bilayer, which is shaped by the physico-chemical environment. These are many factors: composition, phase behaviour, curvature, and tension. Tension acts through lipid packing at the nanoscale.

The planarization changes the energies of the excited and ground states of the fluorophore. This means that the fluorescence properties of Flipper-TR depend on its conformation: fluorescence lifetime, quantum yield, and excitation wavelength.

How does Flipper-TR work?
Flipper-TR inserts in the lipid bilayer. Its mechanosensitive core rotates, sensing the lipid packing. The electron-rich head group confers the plasma membrane specificity... but other versions exist for alternative targeting!

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First, why Flipper-TR? It comes from swimming fins, also called swimming flippers, because of their shape! coined by the first author of the original paper, Marta Dal Molin, at @matilegroup.bsky.social. TR stands for ‘tension reporter’.

Here’s a bit of history: www.unige.ch/campus/numer...

Hello epithelial mechanics fans!! I’m Juanma @juanmagararc.bsky.social 👋 I work on cell mechanics (see celldynamicslab.com) and use Flipper-TR FLIM to probe membrane biophysics in cells.

Join me on this tour about Flipper: what it measures, strengths, advice, cool case studies, and cute drawings!

Espadas, J., Souza, D. P., Hakala, M., García-Arcos, J. M., Tran, J., Kumar, A., Marcuello, C., Merino, A., ..., Toret, C. P., & Roux, A. (2025). Molecular basis for cellular compartmentalization by an ancient membrane fission mechanism. bioRxiv. #EpithelialMechanics
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Mandal, T., Roux, A., & García-Arcos, J. M. (2025). Fluorescence lifetime estimation: a practical approach using Flipper-TR FLIM. bioRxiv. #EpithelialMechanics
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Roffay, C., García-Arcos, J. M., Chapuis, P., López-Andarias, J., Schneider, F., ...., Roux, A., & Mercier, V. (2024). Tutorial: fluorescence lifetime microscopy of membrane mechanosensitive Flipper probes. Nature protocols, 19(12), 3457–3469. #EpithelialMechanicsReview
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Mahecic, D., Carlini, L., Kleele, T., Colom, A., Goujon, A., Matile, S., Roux, A., & Manley, S. (2021). Mitochondrial membrane tension governs fission. Cell reports, 35(2), 108947. #EpithelialMechanics
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García-Arcos, J. M., Mehidi, A., Sanchez-Velasquez, J., Guillamat, P., Tomba, C., Houzet, L., ..., Aumeier, C., & Roux, A. (2025). Adherent cells sustain membrane tension gradients independently of migration. Nature communications, 16(1), 10539. #EpithelialMechanics
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Ragaller, F., Sjule, E., Urem, Y. B., ..., Blom, H., & Sezgin, E. (2024). Quantifying Fluorescence Lifetime Responsiveness of Environment-Sensitive Probes for Membrane Fluidity Measurements. The journal of physical chemistry. B, 128(9), 2154–2167. #EpithelialMechanics
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Roffay, C., Molinard, G., ..., & Roux, A. (2021). Passive coupling of membrane tension and cell volume during active response of cells to osmosis. Proceedings of the National Academy of Sciences of the United States of America, 118(47), e2103228118. #EpithelialMechanics
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Straková, K., López-Andarias, J., Jiménez-Rojo, N., ..., Sakai, N., & Matile, S. (2020). HaloFlippers: A General Tool for the Fluorescence Imaging of Precisely Localized Membrane Tension Changes in Living Cells. ACS central science, 6(8), 1376–1385. #EpithelialMechanics
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Licari, G., Strakova, K., Matile, S., & Tajkhorshid, E. (2020). Twisting and tilting of a mechanosensitive molecular probe detects order in membranes. Chemical science, 11(22), 5637–5649. #EpithelialMechanics
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Cool thread with examples of the role of cell junctions in collective cell migration! 🧪

Thanks for following along.

For more such #EpithelialMechanics threads check out our website: epithelialmechanics.github.io

Collective cell migration isn’t just the sum of individual cell movements. It’s a complex, coordinated behavior of cell networks.

How do cells integrate diverse signals from their environment and neighbors into a unified movement? Many intriguing questions remain to be explored.

Cells communicate and coordinate their behaviors through chemical signals, mechanical forces, and cell-cell adhesions to achieve a directional collective migration.

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We found that during collective cell migration, ZO-1 translocates from tight junctions to podosomes, a type of cell-ECM adhesions, in response to ERK activation. ZO-1 at podosomes contributes to traction force generation and cell invasion.

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