Compartmentalizing and sculpting nanovesicles by phase-separated aqueous nanodroplets

FK Sabet and A Bahrami and AH Bahrami, RSC ADVANCES, 12, 32035-32045 (2022).

DOI: 10.1039/d2ra05855c

Phase-separated liquid droplets inside giant vesicles have been intensely studied as biomimetic model systems to understand cellular microcompartmentation and molecular crowding and sorting. On the nanoscale, however, how aqueous nanodroplets interact with and shape nanovesicles is poorly understood. We perform coarse-grained molecular simulations to explore the architecture of compartmentalized nanovesicles by phase-separated aqueous nanodroplets, and their morphological evolution under osmotic deflation. We show that phase separation of a biphasic liquid mixture can form both stable two- compartment and meta-stable multi-compartment nanovesicles. We identify morphological transitions of stable two-compartment nanovesicles between tube, sheet and cup morphologies, characterized by membrane asymmetry and phase-separation propensity between the aqueous phases. We demonstrate that the formation of local sheets and in turn cup-shaped nanovesicles is promoted by negative line tensions resulting from large separation propensities, an exclusive nanoscale phenomenon which is not expected for larger vesicles where energetic contributions of the line tensions are dominated by those of the membrane tensions. Despite their instability, we observe long-lived multi-compartment nanovesicles, such as nanotubules and branched tubules, whose prolonged lifetime is attributed to interfacial tensions and membrane asymmetry. Aqueous nanodroplets can thus form novel membrane nanostructures, crucial for cellular processes and forming cellular organelles on the nanoscale.

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