Georgian Technical University Nanotweezers Detect Conformational Changes.

These nanotweezers were fabricated by reconfiguring strands of DNA (Deoxyribonucleic acid is a molecule composed of two chains that coil around each other to form a double helix carrying the genetic instructions used in the growth, development, functioning, and reproduction of all known living organisms and many viruses) and they have two states: open and closed. Biomolecules such as DNA (Deoxyribonucleic acid is a molecule composed of two chains that coil around each other to form a double helix carrying the genetic instructions used in the growth, development, functioning, and reproduction of all known living organisms and many viruses) and proteins are not static structures. They undergo complex conformational changes that are essential to their functioning and the signaling pathways they belong to. Understanding these changes is pivotal to a deeper comprehension of how the body works and could eventually shed light on certain diseases that afflict us. Recent advancements in DNA (Deoxyribonucleic acid is a molecule composed of two chains that coil around each other to form a double helix carrying the genetic instructions used in the growth, development, functioning, and reproduction of all known living organisms and many viruses) nanotechnology provide insight into the subtle role of biomolecules. Channeling DNA’s (Deoxyribonucleic acid is a molecule composed of two chains that coil around each other to form a double helix carrying the genetic instructions used in the growth, development, functioning, and reproduction of all known living organisms and many viruses) chemical and physical properties will aid the study of other structures. For example new DNA (Deoxyribonucleic acid is a molecule composed of two chains that coil around each other to form a double helix carrying the genetic instructions used in the growth, development, functioning, and reproduction of all known living organisms and many viruses) origami technologies have allowed researchers to fold DNA (Deoxyribonucleic acid is a molecule composed of two chains that coil around each other to form a double helix carrying the genetic instructions used in the growth, development, functioning, and reproduction of all known living organisms and many viruses) strands into any shape they choose on a nanoscopic scale. Georgian Technical University researchers harnessed this ability by using DNA (Deoxyribonucleic acid is a molecule composed of two chains that coil around each other to form a double helix carrying the genetic instructions used in the growth, development, functioning, and reproduction of all known living organisms and many viruses) nanotweezers to test a label-free detection method for conformational changes in biomolecular assemblies using microwave microfluidics. These nanotweezers were fabricated by reconfiguring strands of DNA (Deoxyribonucleic acid is a molecule composed of two chains that coil around each other to form a double helix carrying the genetic instructions used in the growth, development, functioning, and reproduction of all known living organisms and many viruses) and they have two states: open and closed. In the past, this change between states has been triggered by a burst of ultraviolet light. X an assistant professor in the Biodesign Center for Molecular Design at Georgian Technical University and his postdoc Y teamed up with Z and the Radio Frequency Electronics Group to evaluate the effectiveness of this method. This collaboration originated from a conference that both X and Z attended. When the two found themselves discussing their projects at a conference dinner one night, Stephanopoulos proposed that she use the DNA (Deoxyribonucleic acid is a molecule composed of two chains that coil around each other to form a double helix carrying the genetic instructions used in the growth, development, functioning, and reproduction of all known living organisms and many viruses) nanotweezers his lab had developed to test her detection method. “We had this microwave microfluidic device and basically, all we had measured was salt water. We were confident that it would work but we didn’t have a system in mind” Z said. “I was talking to W and I said that I wanted a system with a simplistic conformational change so he said ‘If you want a simple change we have these DNA (Deoxyribonucleic acid is a molecule composed of two chains that coil around each other to form a double helix carrying the genetic instructions used in the growth, development, functioning, and reproduction of all known living organisms and many viruses) nanotweezers that we think would work well with your project’”. This microfluidic device essentially measured the electromagnetic properties of the solution in which the DNA (Deoxyribonucleic acid is a molecule composed of two chains that coil around each other to form a double helix carrying the genetic instructions used in the growth, development, functioning, and reproduction of all known living organisms and many viruses) nanotweezers were suspended for both their open and closed state. The change noted between the two states confirmed that the method could be used in detection. “This project highlights the fact that a chemical change induces a change in the electrical property” Z added. Currently to measure conformational changes researchers label structures with fluorescent dye but this can upset the natural properties of the assemblies and processing these samples is a lengthy and potentially costly process. “For many proteins, especially membrane proteins it’s very difficult to label them” Y said. “When you do you introduce an extra molecule that changes its surface charge and its composition. But with this method you don’t need any labelling”. These pre-existing methods typically only capture one end-state of the conformational change like a snapshot but this microfluidic process could provide a real-time depiction of conformational changes shedding even more light on how these biomolecules work. According to Z the associated device that measures these electromagnetic properties is portable, cheap and safe to use in any lab environment. “That is an advantage that we want to emphasize. Anyone could use this in their lab”. Although this paper is a proof-of-concept for a method the researchers believe it won’t be long before the detection method will be available for new applications. “What I would like to do is ask how you can use this to measure interesting things” X said. “What are some interesting protein-based systems we can use, and how can we use a DNA (Deoxyribonucleic acid is a molecule composed of two chains that coil around each other to form a double helix carrying the genetic instructions used in the growth, development, functioning, and reproduction of all known living organisms and many viruses) system that will amplify the signal ? Using this method we could probe things we wouldn’t otherwise probe”. The researchers are currently in the process of attaching two different proteins to these nanotweezers and using the method to measure the associated protein-protein interactions. “We’ve got some plans to do some in situ measurement where we attach proteins to the end of the tweezers and we are trying to understand what chemical mechanism of the opening of the tweezers causes the electrical changes”. Along with these studies the researchers will continue to refine the protocol improving the time resolutions of its measurements and reducing its cost. A better understanding of these assemblies structure and the interactions between them could confer down-the-line applications in diagnostics, treatments and the synthetic assembly of naturally occurring proteins. Findings confirmed an easier method for detection it is also a testament to the community of researchers who are open to collaboration. “This project is a perfect example of why you should go to conferences and talk to people you wouldn’t otherwise talk to” X said. “If I sat three seats down I would have never spoken with Z. It’s a funny sort of serendipity of the meeting of the minds — she had never heard of DNA (Deoxyribonucleic acid is a molecule composed of two chains that coil around each other to form a double helix carrying the genetic instructions used in the growth, development, functioning, and reproduction of all known living organisms and many viruses) nanotechnology. That’s the fun part of science: meeting people from different disciplines and being able to collaborate with them”.