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Nat Chem. 2016 May;8(5):476-83. doi: 10.1038/nchem.2472. Epub 2016 Mar 21.

Self-assembly of size-controlled liposomes on DNA nanotemplates.

Yang Y1,2, Wang J1,2, Shigematsu H3, Xu W1,2, Shih WM4,5,6, Rothman JE1,2, Lin C1,2.

Author information

1
Department of Cell Biology, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
2
Nanobiology Institute, Yale University, West Haven, Connecticut 06516, USA.
3
Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, Connecticut 06250, USA.
4
Wyss Institute for Biologically Inspired Engineering, Harvard University, Cambridge, Massachusetts 02138, USA.
5
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA.
6
Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA.

Abstract

Artificial lipid-bilayer membranes are valuable tools for the study of membrane structure and dynamics. For applications such as the study of vesicular transport and drug delivery, there is a pressing need for artificial vesicles with controlled size. However, controlling vesicle size and shape with nanometre precision is challenging, and approaches to achieve this can be heavily affected by lipid composition. Here, we present a bio-inspired templating method to generate highly monodispersed sub-100-nm unilamellar vesicles, where liposome self-assembly was nucleated and confined inside rigid DNA nanotemplates. Using this method, we produce homogeneous liposomes with four distinct predefined sizes. We also show that the method can be used with a variety of lipid compositions and probe the mechanism of templated liposome formation by capturing key intermediates during membrane self-assembly. The DNA nanotemplating strategy represents a conceptually novel way to guide lipid bilayer formation and could be generalized to engineer complex membrane/protein structures with nanoscale precision.

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