4.8 Article

Coacervation-Induced Remodeling of Nanovesicles

Journal

JOURNAL OF PHYSICAL CHEMISTRY LETTERS
Volume 14, Issue 19, Pages 4532-4540

Publisher

AMER CHEMICAL SOC
DOI: 10.1021/acs.jpclett.3c00705

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Intrinsically disordered peptides can form biomolecular condensates through liquid-liquid phase separation, which have diverse roles in cells, including inducing large-scale changes in membrane morphology. Coarse-grained molecular dynamics simulations reveal the physical principles governing membrane remodeling by condensates, with variations in interaction strengths leading to various observed membrane transformations. Insights from this study provide crucial guidance for designing (bio)polymers to manipulate membrane morphology in applications such as drug delivery and synthetic biology.
Intrinsically disordered peptides can form biomolecular condensates through liquid-liquid phase separation. These condensates play diverse roles in cells, including inducing large-scale changes in membrane morphology. Here we employ coarse-grained molecular dynamics simulations to identify the most salient physical principles that govern membrane remodeling by condensates. By systematically varying the interaction strengths among the polymers and lipids in our coarse-grained model, we are able to recapitulate various membrane transformations observed in different experiments. Endocytosis and exocytosis of the condensate are observed when the interpolymeric attraction is stronger than polymer-lipid interaction. We find a critical size of the condensate required to exhibit successful endocytosis. Multilamellarity and local gelation are observed when the polymer-lipid attraction is significantly stronger than the interpolymeric attraction. Our insights provide essential guidance to the design of (bio)polymers for the manipulation of membrane morphology in various applications such as drug delivery and synthetic biology.

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