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Home > Press > Researchers embrace imperfection to improve biomolecule transport

Laboratory-engineered membrane defects with edges that spiral downward would give biomolecules like DNA, RNA and proteins no other option than to sink into a nanopore for delivery, sorting and analysis.

Graphic courtesy Manish Shankla
Laboratory-engineered membrane defects with edges that spiral downward would give biomolecules like DNA, RNA and proteins no other option than to sink into a nanopore for delivery, sorting and analysis. Graphic courtesy Manish Shankla

Abstract:
While watching the production of porous membranes used for DNA sorting and sequencing, University of Illinois researchers wondered how tiny steplike defects formed during fabrication could be used to improve molecule transport. They found that the defects – formed by overlapping layers of membrane – make a big difference in how molecules move along a membrane surface. Instead of trying to fix these flaws, the team set out to use them to help direct molecules into the membrane pores.



DNA on graphene steps



Force-guided delivery of DNA molecule to a nanopore

Researchers embrace imperfection to improve biomolecule transport

Champaign, IL | Posted on August 8th, 2019

Their findings are published in the journal Nature Nanotechnology.

Nanopore membranes have generated interest in biomedical research because they help researchers investigate individual molecules – atom by atom – by pulling them through pores for physical and chemical characterization. This technology could ultimately lead to devices that can quickly sequence DNA, RNA or proteins for personalized medicine.

“Molecular dynamics simulations let us watch what is happening while simultaneously measuring how much force is required to get the molecule to clear a step,” Aksimentiev said. “We were surprised to find that it takes less force to move a molecule down a step than up. Although it may seem intuitive that gravity would make stepping down easier, it is not the case here because gravity is negligible at the nanoscale, and the force required to move up or down should be the same.”

Aksimentiev said team members originally thought they could use concentric defect patterns that form around the pores to force the molecules down, but their simulations showed the molecules congregating along the edges of the steps. That is when it dawned on them: A defect with edges that spiral into a pore, combined with an applied directional force, would give the molecule no other option than to go into the pore – kind of like a drain.

“This way, we can drop molecules anywhere on the membrane covered with these spiral structures and then pull the molecules into a pore,” he said.

The researchers have not yet produced a membrane with spiral defects in the laboratory, but that task may be easier than trying to rid a graphene membrane of the current molecule-immobilizing step defects, they said.

“When manufactured at scale, defect-guided capture may potentially increase the DNA capture throughput by several orders of magnitude, compared with current technology,” Shankla said.

“After a long development process, we are excited to see this principle used in a variety of other materials and applications such as delivery of individual molecules to reaction chambers for experiments,” the researchers said.

The National Institutes of Health, National Science Foundation and the Dutch Research Council supported this research.

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Contacts:
LOIS YOKSOULIAN
PHYSICAL SCIENCES EDITOR
217-244-2788


Aleksei Aksimentiev
217-333-6495

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The paper “Step-defect guided delivery of DNA to a graphene nanopore” is available online and from the U. of I. News Bureau. DOI: 10.1038/s41565-019-0514-y:

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