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Tailoring Interleaflet Lipid Transfer with a DNA-based Synthetic Enzyme.
Diana Sobota1, Himanshu Joshi2, Alexander Ohmann1
1Cavendish Laboratory, University of Cambridge, JJ Thomson Avenue, Cambridge CB3 0HE, United Kingdom.
Nano Letters
|May 7, 2020
Summary
Researchers created a DNA construct that self-assembles and inserts into lipid membranes, facilitating controlled lipid transfer. This artificial enzyme mimics natural proteins, offering tunable control over membrane composition.
Area of Science:
- Biochemistry
- Molecular Biology
- Materials Science
Background:
- Lipid membranes are essential for all living systems, and controlling their structure is vital for artificial systems.
- Designing protein-inspired systems for membrane manipulation remains a significant challenge.
Purpose of the Study:
- To develop a functional nucleic acid construct capable of self-assembly and insertion into lipid membranes.
- To achieve controlled lipid transfer between membrane leaflets using a DNA-based enzyme.
- To mimic the stimuli-responsive behavior of natural lipid-flipping proteins.
Main Methods:
- Designed a nucleic acid construct incorporating hydrophobic modifications for membrane interaction.
- Investigated the self-assembly and insertion of the DNA construct into lipid membranes.
- Analyzed the rate of interleaflet lipid transfer induced by the DNA construct.
- Studied the effect of divalent ion concentration on lipid transfer regulation.
Main Results:
- Successfully developed a DNA construct that self-assembles and inserts into lipid membranes.
- Demonstrated controlled interleaflet lipid transfer mediated by the DNA construct.
- Showed that lipid transfer rate is influenced by DNA structure, hydrophobic modifications, and lipid interactions.
- Regulated lipid transfer levels by altering divalent ion concentration, mimicking protein behavior.
Conclusions:
- A novel DNA-based enzyme was engineered to control lipid transfer in membranes.
- The rational design of nucleic acid constructs allows for precise manipulation of membrane lipid composition.
- This approach offers a new avenue for creating stimuli-responsive artificial membrane systems.

