Spatial Organization of Biological Fuctions | BPS Thematic Meeting

Spatial Organization of Biological Functions Meeting

Wednesday Speaker Abstracts

UNVEILING THE ROLE OF MEMBRANES IN MODULATING BIOMOLECULAR CONDENSATE SIZE Karthika S Nair 1 ; Sreelakshmi Radhakrishnan 1 ; Harsha Bajaj 1 ; 1 CSIR National Institute for Interdisciplinary Science and Technology, Trivandrum, India Biomolecular condensates are dynamic, membrane-less compartments formed via phase separation, enabling spatial and temporal regulation of essential cellular processes. Their tunable material properties facilitate rapid cellular responses, while their dysregulation is increasingly implicated in disease. While the role of liquid–liquid phase separation (LLPS) in cellular organization is increasingly being uncovered, their interactions with membranes remain largely unexplored. To investigate this interplay, we assemble condensates in cell-mimetic systems. Here, we reconstitute nucleotide–peptide condensates within semipermeable Giant Unilamellar Vesicles (GUVs) with defined lipid compositions. This system allows precise control over condensate formation and facilitates the study of condensate–membrane interplay. By engineering electrostatic interactions, we observe that weakly interacting condensates induce membrane budding, while strong interactions cause membrane wrinkling. FRAP analysis quantifies slowed membrane diffusion due to condensate interactions in membrane wrinkling, while TEM and high-resolution imaging confirm condensate embedding within wrinkled membrane folds. Our findings suggest that charge-mediated interactions between condensates and membranes modulate droplet dynamics by altering wettability and inducing membrane curvature, similar to condensate-driven budding observed in protein storage vacuoles. Similarly, our observations of reduced membrane diffusion align with similar effects reported for ribonucleoprotein condensates at the endoplasmic reticulum. Finally, our findings elucidate the mechanistic role of lipid bilayers in modulating condensate size, providing critical insights into the biophysical principles governing condensate nucleation and spatial organization in cellular environments. References : 1) Karthika S Nair, Sreelakshmi Radhakrishnan, and Harsha Bajaj, Dynamic Control of Functional Coacervates in Synthetic Cells, ACS Synthetic Biology 2023, 12 (7), 2168–2177.2) Sreelakshmi Radhakrishnan, Karthika S Nair, Samir Nandi, Harsha Bajaj. Engineering Semi-Permeable Giant Liposomes, Chemical Communications, 2023, 59 (93), 13863–138663) Karthika S Nair, Sreelakshmi Radhakrishnan, Harsha Bajaj, Dynamic Duos: Coacervate-Lipid Membrane Interactions in Regulating Membrane Transformation and Condensate Size, Small, 2025, 2501470.

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