Membrane-anchored polyproline provides controlled micro-domain formation and permeability in lipid vesicles

12 June 2025, Version 3
This content is a preprint and has not undergone peer review at the time of posting.

Abstract

This study introduces the synthesis of a new class of lipopolymers, composed of L-proline monomer units and a phos-pholipid initiator. By anchoring polyproline chains to the membrane, reversible phase separation was achieved, with clusters forming at high temperature and dispersing upon cooling. Confocal microscopy and FRAP analyses confirmed micro-domain formation after heating and restored diffusion property after cooling, demonstrating a dynamic control over local membrane composition. Importantly, the micro-domains enhanced membrane permeability, enabling size-controlled release of encapsulated molecules, including synthetic polymers and enzymes. The system showed adapt-ability across various membrane compositions, suggesting its potential for applications in drug delivery or synthetic biology, especially for mimicking protein-like behavior in lipid vesicles.

Keywords

Lipopolypeptide
LCST
Proline
Thermoresponsive liposomes
Membrane destabilization

Supplementary materials

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Supplementary Materials
Description
Part I. Supplementary experimental methods Materials Ring-opening polymerization of Proline N-Carboxyanhydrides Preparation of Giant Unilamelar Vesicles (GUVs) Part II. Supplementary characterization methods NMR Size Exclusion Chromatog-raphy UV-vis spectroscopy Dynamic Light Scattering (DLS) Confocal Imaging Fluorescence Recovery after Photobleaching (FRAP) Supplementary schemes, figures and ta-bles Refer-en-ces
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