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Phospholipids self-assemble into cuboid vesicles

Cubes could be developed for mechanically responsive drug delivery devices

by Celia Henry Arnaud
May 8, 2017 | A version of this story appeared in Volume 95, Issue 19

These models depict the structure of cuboid phospholipid vesicles.
Credit: Andreas Zumbuehl/U. Fribourg
Cuboid phospholipid vesicles could be used for mechano-responsive drug delivery.

When lipids self-assemble as vesicles, they typically form spheres because that shape minimizes surface tension. Only a few nonspherical systems have been made to date, and many of those systems require templates to scaffold the structure. Now, a team led by Andreas Zumbuehl of the University of Fribourg reports a 1,2-diamidophospholipid that self-assembles into cube-shaped vesicles without a scaffold (Angew. Chem. Int. Ed. 2017, DOI: 10.1002/anie.201701634). Hydrogen bonding between amide groups in the lipid leads to rigid membranes. Wide-angle X-ray scattering measurements suggest that the membrane packs in a herringbone pattern, the tightest bilayer packing known. Because of their stiffness, the membranes must be heated above their melting temperature, where they are in a fluid state, to form vesicles. When the vesicles are then cooled below their melting temperature, they adopt a cubic shape that maximizes flat surfaces and minimizes edges. The researchers want to use the cubes to help design drug delivery devices that respond to mechanical triggers. “The cubes themselves are probably too frail for this purpose because of their very long defect lines along the edges,” Zumbuehl says. “But they’ve taught us a lot about the physics needed for a next-generation mechano-responsive drug delivery container.”


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