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Controlling aggregation of cholesterol-modified DNA nanostructures.
Alexander Ohmann1, Kerstin Göpfrich1,2, Himanshu Joshi3
1Cavendish Laboratory, University of Cambridge, JJ Thomson Avenue, Cambridge CB3 0HE, UK.
Nucleic Acids Research
|October 24, 2019
Summary
Controlling DNA nanostructure aggregation is key for membrane interactions. This study shows DNA overhangs can tune cholesterol tag aggregation, enabling precise control of DNA nanodevices.
Area of Science:
- Biotechnology
- Nanotechnology
- Biophysics
Background:
- DNA nanostructures offer programmable control for interfacing with biological membranes.
- Hydrophobic modifications, like cholesterol, are crucial for this membrane interaction.
- However, these modifications often cause aggregation, hindering structural control.
Purpose of the Study:
- To investigate the aggregation behavior of cholesterol-modified DNA nanostructures.
- To identify factors influencing this aggregation.
- To develop a method for controlling aggregation in DNA nanodevices.
Main Methods:
- Non-denaturing polyacrylamide gel electrophoresis
- Dynamic light scattering
- Confocal microscopy
- Atomistic molecular dynamics simulations
Main Results:
- Cholesterol-tagged single-stranded DNA (ssDNA) aggregation is sequence-dependent.
- For assembled DNA constructs, tag number and position are key factors.
- DNA nucleotides shield hydrophobic moieties, a phenomenon observed via molecular dynamics simulations.
- ssDNA overhang length controls cholesterol-mediated aggregation.
Conclusions:
- A method to control cholesterol-mediated aggregation in DNA nanostructures was developed.
- This control enhances the structure-function relationship of membrane-interfacing DNA constructs.
- Enables more precise application of DNA nanodevices in research and biomedicine.
