DNA Origami Nanodevice Maps Protein Interactions | Nanowerk

A newly developed DNA origami nanodevice is enabling researchers to study how mechanical force impacts protein interactions, revealing previously unseen binding partnerships, according to a report published today by researchers at multiple institutions.

The device, detailed in a recent article in Nature, utilizes the programmable mechanics of DNA hairpins and the defined geometry of DNA origami to apply controlled forces to proteins. This allows for the observation of protein behavior under piconewton tension – a scale previously difficult to achieve with traditional biochemical analysis techniques.

Researchers focused initially on the R1-R2 segment of the talin1 rod domain as a model protein. Their work demonstrated that this segment unfolds reversibly under tension, exposing binding sites for vinculin, a cytoskeletal protein. Electron microscopy confirmed these tension-dependent conformational changes, and biochemical analysis validated the enhanced vinculin binding under applied force.

The innovation lies in the device’s ability to perform bulk biochemical analysis, unlike many existing methods that are limited to single-molecule studies. Using the nanodevice in pull-down assays with cell lysates, the team identified filamins as novel tension-dependent talin binders. This suggests a previously unknown role for filamins in cellular responses to mechanical stress.

“Some proteins only reveal their full function when they are physically pulled,” researchers noted in a spotlight article published by Nanowerk. The device’s tunable DNA hairpin springs allow for the stretching of millions of protein copies simultaneously, facilitating the discovery of these force-dependent interactions.

The technology builds on prior work in DNA nanotechnology, leveraging the precision offered by DNA origami – a method of folding DNA into specific shapes – to create a nanoscale platform for manipulating molecules. A related technique, described in a recent PubMed article, utilizes DNA origami “rubbings” to map the two-dimensional distribution of membrane proteins, further demonstrating the versatility of DNA origami in protein research.

Beyond studying protein interactions, similar DNA origami-based devices are being developed for other applications, including precise electrical measurements of single proteins, as reported by Nanowerk. These cages constrain proteins to preferred orientations on electrodes, improving measurement precision and enabling the detection of subtle structural changes.

The Nature study concludes that the DNA nanodevice represents a valuable tool for studying mechanosensitive proteins on a biochemical scale, but does not indicate any immediate plans for further research or clinical applications. The research team has not yet responded to requests for comment regarding the potential for commercialization of the technology.