We find that condensate interfaces catalyze nucleation of fibrils (as shown by Paolo Arosio, Evan Spruijt, Cliff Brangwynne) but that the interiors of condensates suppress fibril formation and growth. The fibrils grow from the dilute phase! Stabilizing condensates suppresses fibril growth.

Postdocs @tapojyotidas.bsky.social and Fatima Zaidi from my lab tackled this question with Mina Farag and Kiersten Ruff in Rohit's lab. @priya-r-banerjee.bsky.social and Tharun Mahendran and Anruag Singh came up with a neat condensate efflux assay. Collaboration with Paul Taylor on cellular data.

Using kinetic models inspired by Tuomas Knowles, we predicted that efflux of material from metastable condensates becomes rate-limiting for fibril formation. Efflux slows as metastability increases. Experiments with @priya-r-banerjee.bsky.social confirmed these predictions.

This observation led us to investigate the impact of sugar modifications on RNA condensation. We found that 2'-O-methylation reduces the driving force of RNA phase transitions and promotes reversibility, suggesting that sugar modifications serve as a tunable switch for RNA condensation. 2/2

@tharun-mahendran.bsky.social

For our first scientific session spotlight we are "Peeking away from the lampost" with Dr. Rohit Pappu as he joins us to discuss intrinsically disordered proteins. @rohitpappu68.bsky.social @biophysicalsoc.bsky.social #bps2025 youtu.be/pAP2lBWBiGU