Nov. 8 — What do you get when you cross an art form with something found in all living organisms?
It may sound unusual, but DNA origami is something that has been explored in the scientific community for the last 10 years.
DNA is a string of four nucleotide bases (A, T, G and C), each of which pairs only with one other base (A with T and G with C). In DNA origami, researchers take a long single strand of DNA (picture a ladder sawed in half vertically), and fold it into a shape using staple strands that have the corresponding bases. Everything from smiley faces to robots has been made using this method. While those are 2D, 3D shapes can also be made.
Aleksei Aksimentiev’s group at the University of Illinois at Urbana-Champaign has been using this method to simulate membrane channels using the Blue Waters supercomputer at the National Center for Supercomputing Applications (NCSA) on the University of Illinois campus. In their most recent paper, published in ACS Nano, members of Aksimentiev’s group, Chen-Yu Li, a graduate student at the University of Illinois and Jejoong Yoo, a postdoctoral fellow with the Center for the Physics of Living Cells, were able to create the largest synthetic membrane channel yet.
“The largest membrane channel ever made is as big as the largest pores that are found in biology, so in a sense we span all of the range of the biological channels in nature but mimic them in DNA,” Aksimentiev says, “which offers interesting possibilities—how do we make them selective, how do we add gates that open and close, stuff like that.”
To understand why this is such a big deal, first you have to understand cells. Encapsulating each of our cells is a membrane made of lipids and proteins. We also have pores in the membrane of certain cells. Some membranes allow ions to pass through and some allow water to pass through.
To build a synthetic channel that has the same functionality as a biological channel or that does something similar, the traditional approach is to try to take what already exists and introduce small modifications. However, it’s difficult if engineers want to completely redesign the channel since it’s still unknown how to solve problems that involve folding the membrane protein.
Aksimentiev’s collaborator in England, Ulrich Keyser at the University of Cambridge, came up with the idea to use DNA instead of modifying the protein; the DNA structures would be modified so they could be compatible with the membrane. They were able to put the modified DNA structures in the membrane but they still had a problem—they didn’t know how to make the channels work.
“That’s where we came in with Blue Waters, we decided to simulate these channels,” Aksimentiev says. “One of the things we’ve discovered is that water can also flow around the DNA helix threaded through a biological membrane, which led us to a single DNA helix design. This smallest ever synthetic DNA channel passes ions as biological ion channels do.”
There are a few possible applications. When the technology is perfected, researchers could explore utilizing it for drug delivery by modifying the channels to recognize selective tissues and open up the membrane. It could also be used in artificial tissues to give the cells a way to communicate.
Source: Susan Szuch, NCSA