Cooperative Self-Assembly of Lipid–Polymer Hybrids Stabilizing Highly Ordered Bicontinuous Cubic Phases in Air

There is a long-term interest in creating artificial biomimetic membranes where self-assembled phospholipid bilayers are selectively permeabilized by synthetic channel-like molecules. One example is the coassembly of amphiphilic block copolymers with phospholipids into a hybrid membrane. Hybrid phospholipid block copolymer bilayers display many properties, seen in biomembranes such as selective transport phenomena, synergistic elastic properties, and structural phase transformations. Just like in biomembranes, these fundamental properties of hybrid bilayers are often regulated by lateral phase separation. Understanding the molecular and physical cues that determine the formation of rafts or domains in hybrid membranes, their size, and morphology is paramount to elucidating and programming their function. Employing a combination of coarse-grained molecular dynamics simulations and high-resolution cryogenic electron microscopy, we discovered that phosphatidylcholine-cholesterol bilayers hybridized with poly(butadiene-b-ethylene oxide) develop two distinct phase-separated morphologies. At molar fractions of polymer above 10 mol % the expected molecular distribution into lipid-rich and polymer-rich domains is observed. However, at low polymer content, a new structure develops in which the bilayer leaflets unzip (but remain continuous) to incorporate nanodomains of hydrophobic butadiene globules. We conjecture that unzipping is energetically more favorable than sustaining the hydrophobic mismatch between butadiene blocks and phospholipid acyl chains. These findings offer new insights into the morphology of biomembranes upon the insertion of transmembrane proteins with bulky hydrophobic residues.

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Nanostructure Formation in Glycerolipid Films during Enzymatic Hydrolysis: A GISAXS Study

Freire,

Tran,

Debas

et al. 2024

ACS Appl. Mater. Interfaces

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Responsive nanostructured films from food-grade lipids can be valuable for food, pharmaceutical, and biotechnological science. Lyotropic liquid crystalline structures that respond to enzymes in their environment can, for instance, be innovated as drug delivery platforms or biosensors. However, the structural changes that such films undergo during enzymatic reactions with lipase are not yet understood. This work demonstrates the preparation of mesostructured lipid films from the food-grade lipids glycerol monooleate (GMO) and triolein on silicon wafers and their digestion with pancreatic lipase using time-resolved synchrotron grazing incidence small-angle X-ray scattering (GISAXS). The film structure is compared with the corresponding GMO/triolein bulk phases in excess water. Increasing the GMO/triolein ratio in the film makes it possible to modulate the structure of the films from oil coatings to inverse hexagonal and inverse bicontinuous cubic films. Pancreatic lipase triggered swelling of the internal film nanostructure and eventually structural transformation inside the film. Orientation and reorientation of the internal film structure relative to the silicon wafer surface were observed during the preparation of the films and their digestion. The findings contribute to the understanding of self-assembly in thin films and guide the development of enzyme-responsive coatings for the functional modification of various substrates.

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Cooperative Self-Assembly of Lipid–Polymer Hybrids Stabilizing Highly Ordered Bicontinuous Cubic Phases in Air

Cited by 3 publications

References 58 publications

Structural characterization of lateral phase separation in polymer–lipid hybrid membranes

Structural characterization of lateral phase separation in polymer–lipid hybrid membranes

Lipid Membrane Leaflets Unzip upon Hybridization with Polymer-Rich Nanodomains

Nanostructure Formation in Glycerolipid Films during Enzymatic Hydrolysis: A GISAXS Study

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