Spatial Presentation of Cholesterol Units on a DNA Cube as a Determinant of Membrane Protein-Mimicking Functions

Abstract

Cells use membrane proteins as gatekeepers to transport ions and molecules, catalyze reactions, relay signals, and interact with other cells. DNA nanostructures with lipidic anchors are promising as membrane protein mimics because of their high tuneability. However, the design features specifying DNA nanostructure's functions in lipid membranes are yet to be fully understood. Here, we show that altering patterns of cholesterol units on a cubic DNA scaffold dramatically changes its interaction mode with lipid membranes. This results in simple design rules that allow a single DNA nanostructure to reproduce multiple membrane protein functions: peripheral anchoring, nanopore behavior and conformational switching to reveal membrane-binding units. Strikingly, the DNA-cholesterol cubes constitute the first open-walled DNA nanopores, as only a quarter of their wall is made of DNA. This functional diversity can increase our fundamental understanding of membrane phenomena, and results in sensing, drug delivery and cell manipulation tools. ASSOCIATED CONTENT Supporting Information. This material is available free of charge via the Internet at http://pubs.acs.org. DNA cage design and assembly, lipid vesicle preparation, membrane-binding study, dye-influx assay and molecular dynamic simulations.

Exploring the Relationship between BODIPY Structure and Spectroscopic Properties to Design Fluorophores for Bioimaging

“…We believe this is due to degradation upon ionisation. [36] GUVs were prepared by electroformation by using Nanion Vesicle Prep Pro equipment. Twoa liquots of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) (6 mL, 25.4 mm in CHCl 3 )w ere deposited on an indium tin oxide glass plate inside two rubber rings and the solvent left to evaporate.…”

“…Confocal microscopy [36] Microscopic analyses were carried out by using the Leica SPEinv (inverted SPE) microscope (vesicles) or the Leica TCS SP8 (cells), with single-photon irradiation with sequential scanning. With this setup, filters are not needed.…”

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

“…To transport these therapeutic molecules into target cells and tissues, scientists have devised a number of nanocarriers, such as nanoparticles and DNA nanostructures . Framework nucleic acids (FNAs), a wide variety of robust DNA nanoframes (for example, tetrahedrons, pyramids, and cubes), display unique biophysical and biochemical properties, and have proven ideal nanocarriers for intracellular transport of molecular payloads, including proteins, anticancer drugs, siRNAs, and ASOs . However, the activation of the FNA nanocarriers in vivo for controllable cargo release once they enter cells remains a challenge.…”

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

“…To transport these therapeutic molecules into target cells and tissues, scientists have devised a number of nanocarriers, such as nanoparticles and DNA nanostructures . Framework nucleic acids (FNAs), a wide variety of robust DNA nanoframes (for example, tetrahedrons, pyramids, and cubes), display unique biophysical and biochemical properties, and have proven ideal nanocarriers for intracellular transport of molecular payloads, including proteins, anticancer drugs, siRNAs, and ASOs . However, the activation of the FNA nanocarriers in vivo for controllable cargo release once they enter cells remains a challenge.…”