Synthetic cell membrane channels made up of DNA can be opened and closed with a switch

Synthetic cell membrane channels made up of DNA can be opened and closed with a switch

The graphic shows the bilayer structure of the living cell membrane, which is made up of phospholipids. Phospholipids consist of a hydrophilic or hydrophilic head and a hydrophobic or hydrophobic tail. The hydrophobic tails are sandwiched between two layers of hydrophilic heads. In the center, a channel is shown that allows the transport of biomolecules. The new study describes a process for creating artificial channels using fragments of DNA that insert into cell membranes and allow the reverse transit of various goods, including ions and proteins. Credit: Biodesign Institute at Arizona State University

Just as countries import a wide range of consumer goods across national borders, live cells are engaged in active import and export business. Its ports of entry are well-developed transport channels embedded in the cell’s protective membrane. Regulating the types of cargo that can pass through the borderlands of which the two-layer cell membrane is formed is essential for proper functioning and survival.

In new research, ASU professor Hao Yan, along with colleagues at ASU and international collaborators from University College London, describe the design and construction of artificial membrane channels, designed using short segments of DNA. DNA structures frequently behave in the manner of normal cell channels or pores, providing selective transport of ions, proteins, and other cargo, with enhanced features not available in their naturally occurring counterparts.

These innovative DNA nanochannels may one day be applied in a variety of scientific fields, from biosensing and drug delivery applications to creating artificial cell networks capable of autonomous capture, concentration, storage and delivery of microscopic charges..

“Many of the biological pores and channels have reversible gates to allow passage of ions or molecules,” Yan says. Here we simulate these natural processes of engineering DNA nanopores that can close and open in response to an external ‘switch’ or ‘lock’ molecules.

Professor Yan is the Milton D. Glick Distinguished Professor of Chemistry and Biochemistry at ASU and directs the Biodesign Center for Molecular Design and Biomimetics. He is also a professor in the Arizona State University School of Molecular Sciences.

The results of the search appear in the current issue of the magazine Nature Communications.

All living organisms cells Encapsulated in a unique biological structure Cell membrane. The scientific term for such membranes is phospholipid bilayer, which means that the membrane consists of phosphate molecules bound to a lipid or lipid component to form an outer and inner membrane layer.

The inner and outer membrane layers are similar to the inner and outer walls of a room. But unlike ordinary walls, the space between the inner and outer surfaces is fluid, like the sea. Moreover, cell membranes are said to be semi-permeable, allowing certain cargo to enter or exit the cell. This transfer typically occurs when the transient cargo binds to another molecule, altering the dynamics of the channel structure to allow entry into the cell, such as opening the Panama Canal to an extent.

Semi-permeable cell membranes are essential to protect sensitive components inside the cell from a hostile environment outside, while allowing the transit of ions, nutrients, proteins, and other vital biomolecules.

The researchers, including Yan, have discovered the potential to create synthetically selective membrane channels, using a technique known as DNA nanotechnology. The basic idea is simple. The double strands of DNA that make up everyone’s genetic blueprint living creatures They are held together by the base pairing of the molecule’s four nucleotides, labeled A, T, C, and G. A simple rule applies, which is that A nucleotides always pair with a T and a C with a G. strand with CAAGAGC.

DNA base pairing allows for the artificial construction of a nearly unlimited array of 2D and 3D nanostructures. Once the structure has been carefully designed, usually with computer aid, the DNA segments can be mixed together and will self-assemble in solution to the desired shape.

However, creating a semi-permeable channel using DNA nanotechnology has proven to be a troublesome challenge. Conventional techniques have failed to replicate the structure and capabilities of nature-made membrane channels, and synthetic DNA nanopores generally allow cargo transport in only one direction.

The new study describes an innovative method that allows researchers to design and build an artificial membrane channel pore size It allows a greater load to be transferred than normal cell channels can. In contrast to previous efforts to create DNA nano-holes that are glued to membranes, the new technique builds the channel structure step-by-step, by assembling the component DNA segments horizontally with respect to the membrane, rather than vertically. This method allows the construction of nanopores with wider openings, which allows for the transport of a larger range of biomolecules.

Furthermore, the DNA design of the channel allows it to be opened and closed selectively via a hinged cover fitted with a lock-and-key mechanism. The ‘switches’ consist of sequence-specific DNA strands that attach to the cap of the channel and induce it to open or close.

In a series of experiments, the researchers demonstrated the ability of the DNA channel to successfully transport cargo of various sizes, from small dye molecules to folded protein structures, some larger than normal pore dimensions. membrane channels.

Researchers used Atomic force microscope and transmission electron microscopy to visualize the resulting structures, and ensure that they conform to the original design specifications of the nanostructures.

Fluorescent dye molecules were used to verify that DNA channels successfully penetrated and implanted themselves through the cell’s lipid bilayer, successfully providing selective entry for transport molecules. Transfer carried out within 1 hour of Channel which is a significant improvement over previous DNA nanopores, which typically require 5-8 hours for complete biomolecule transit.

DNA nanochannels can be used to capture and study proteins, closely examine their interactions with the biomolecules to which they bind, or study the rapid and complex folding and unfolding of proteins. These channels can also be used to exert precise control over biomolecules entering cells, providing a new window on target drug delivery. Many other potential applications likely arise from the newly discovered ability to design self-assembled artificial transport channels.


Scientists create artificial cells that mimic the ability of living cells to capture, process and expel materials


more information:
Swarup Dey et al, A reverse transmembrane channel for protein transport made of DNA, Nature Communications (2022). DOI: 10.1038 / s41467-022-28522-2

Introduction of
Arizona State University


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