The use of magnetic nanoparticles
in biomedical applications provides are a wealth of opportunities.
Nonetheless, to truly understand the interactions of these materials
in biological media, detailed characterization is necessary with these
complex systems. This Feature highlights some “best practices”
in the analytical techniques and challenges in the measurement of
the properties of these materials.
DNA nanotechnology has emerged as a promising method for designing spontaneously inserting and fully controllable synthetic ion channels. However, both insertion efficiency and stability of existing DNA-based membrane channels leave much room for improvement. Here, we demonstrate an approach to overcoming the unfavorable DNA−lipid interactions that hinder the formation of a stable transmembrane pore. Our all-atom MD simulations and experiments show that the insertion-driving cholesterol modifications can cause fraying of terminal base pairs of nicked DNA constructs, distorting them when embedded in a lipid bilayer. Importantly, we show that DNA nanostructures with no backbone discontinuities form more stable conductive pores and insert into membranes with a higher efficiency than the equivalent nicked constructs. Moreover, lack of nicks allows design and maintenance of membrane-spanning helices in a tilted orientation within the lipid bilayer. Thus, reducing the conformational degrees of freedom of the DNA nanostructures enables better control over their function as synthetic ion channels.
High‐resolution analysis of biomolecules has brought unprecedented insights into fundamental biological processes and dramatically advanced biosensing. Notwithstanding the ongoing resolution revolution in electron microscopy and optical imaging, only a few methods are presently available for high‐resolution analysis of unlabeled single molecules in their native states. Here, label‐free electrical sensing of structured single molecules with a spatial resolution down to single‐digit nanometers is demonstrated. Using a narrow solid‐state nanopore, the passage of a series of nanostructures attached to a freely translocating DNA molecule is detected, resolving individual nanostructures placed as close as 6 nm apart and with a surface‐to‐surface gap distance of only 2 nm. Such super‐resolution ability is attributed to the nanostructure‐induced enhancement of the electric field at the tip of the nanopore. This work demonstrates a general approach to improving the resolution of single‐molecule nanopore sensing and presents a critical advance towards label‐free, high‐resolution DNA sequence mapping, and digital information storage independent of molecular motors.
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