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oai:figshare.com:article/34024583 2026-09-29T14:37:27Z category_1 category_4 category_915 category_12 category_14 category_15 category_734 category_106 portal_63 item_type_6 month_year_09_2026

Transmembrane Coupling of Protein Condensates via Membrane-Mediated Interactions: A Simulation Study B. Rusen Argun (25137458) Jeanne Stachowiak (19066754) Pengyu Ren (224961) Biophysics Biochemistry Physical Sciences not elsewhere classified Cell Biology Molecular Biology Neuroscience Biological Sciences not elsewhere classified Science Policy using cooke ’ two mechanisms could simple geometric picture partially overlapping state pair instead settles effective bending modulus two condensates across protein condensates sitting wetting condensate suppresses membrane tension flattens wetting mechanism bending undulations undulation modes thin film smaller condensate results indicate resulting ring opposite surfaces opposite side one condensate mediated interactions mediated interaction mean force like shape induced interaction even though driven mainly condensate wets cannot touch also compare Recent experiments show that protein condensates sitting on opposite surfaces of a flat lipid membrane move together and prefer to overlap, even though they cannot touch each other. This points to an indirect, membrane-mediated interaction. Two mechanisms could be responsible: a curvature-induced interaction, which is energetic in origin, and a fluctuation-induced interaction, which is entropic. Here we study both with coarse-grained molecular dynamics simulations, using Cooke’s implicit-solvent lipid model together with a generic bead–spring polymer model for the condensate. We compute the potential of mean force between two condensates across the membrane. For condensates of the same size, full overlap is unfavorable, and the pair instead settles into a partially overlapping state that bends the membrane into an S-like shape. When the two condensates differ strongly in size, full overlap becomes favorable. We explain this with a simple geometric picture. The condensate wets the membrane as a thin film and imposes curvature only along its rim, while membrane tension flattens the membrane under its interior. The resulting ring of curvature can trap a smaller condensate on the opposite side. We also compare the bending undulations and the effective bending modulus of a bare membrane, a membrane with one condensate, and a membrane with condensates on both sides. A wetting condensate suppresses the undulation modes and stiffens the membrane, but whether this makes overlap entropically favorable remains inconclusive. Our results indicate that the coupling is driven mainly by curvature, and that it depends on the wetting mechanism and on the membrane tension. 2026-09-29T00:00:00Z Text Journal contribution 10.1021/acs.jpcb.6c04719.s001 https://figshare.com/articles/journal_contribution/Transmembrane_Coupling_of_Protein_Condensates_via_Membrane-Mediated_Interactions_A_Simulation_Study/34024583 CC BY-NC 4.0