DNA Nanostructure-Programmed Like-Charge Attraction at the Cell-Membrane Interface

Abstract

Cell entry of anionic nano-objects has been observed in various types of viruses and self-assembled DNA nanostructures. Nevertheless, the physical mechanism underlying the internalization of these anionic particles across the negatively charged cell membrane remains poorly understood. Here, we report the use of virus-mimicking designer DNA nanostructures with near-atomic resolution to program “like-charge attraction” at the interface of cytoplasmic membranes. Single-particle tracking shows that cellular internalization of tetrahedral DNA nanostructures (TDNs) depends primarily on the lipid-raft-mediated pathway, where caveolin plays a key role in providing the short-range attraction at the membrane interface. Both simulation and experimental data establish that TDNs approach the membrane primarily with their corners to minimize electrostatic repulsion, and that they induce uneven charge redistribution in the membrane under the short-distance confinement by caveolin. We expect that the nanoscale like-charge attraction mechanism provides new clues for viral entry and general rules for rational design of anionic carriers for therapeutics.

Advances in DNA Origami–Cell Interfaces

“…It was simultaneously demonstrated that these nanostructures could translocate into the nucleus where the 3D triangle displayed greater accumulation. The triangle structures possess structural features, such as rigid edges and sharp vertices, that are consistent with those of other studies, as noted below . In addition, it was found that the efficiency of DOX loading onto DNA origami nanostructures could be increased by around 15 % (from 68.3, 71.8 and 70.5 % to 85.8, 86.2 and 86.3 % for cross, rectangle and triangle shapes, respectively) if the reaction was performed at an elevated temperature of 37 °C, relative to the results obtained at commonly used room temperature.…”

“…Although the dependence on structural parameters of internalisation of DNA origami structures into cells has been investigated, to some degree, as discussed above, the structure‐mediated uptake mechanisms remain unknown. Using simulations, Ding and co‐workers found that tetrahedral DNA nanostructures primarily attacked the membrane with their corners and that this mode was common to HB structures (Figure D) . Charge redistribution on the plasma membrane with the approach of the origami structure also plays an important role in the internalisation process.…”

“…Adapted with permission from ref. . Copyright: 2018, American Chemical Society (further permissions related to the material excerpted should be directed to the ACS).…”

Environment‐Recognizing DNA‐Computation Circuits for the Intracellular Transport of Molecular Payloads for mRNA Imaging

“…Furthermore, FNA‐2 is almost not colocalized with the LysoTracker green dye (Figure a, the Ctrl line). According to the two‐step disassembly process of FNA‐2 verified in PAGE (Figure a), we rationally deduce that during caveolin‐dependent receptor‐mediated endocytosis (Supporting Information, Figure S17), FNA‐2 undergoes structural changes in the lysosomal compartments where ATP and H + are abundant, followed by an escape into the cytoplasm to respond to the target mRNA …”

Attack on the Cell Membrane: The Pointy Ends of DNA Nanostructures Lead the Way

“…In this issue of ACS Central Science , Fan and colleagues combined molecular simulations and experiments to examine the like-charge, attraction-mediated interactions at the interface between DNA nanostructures and the cell membrane. 1 …”