Researchers create self-assembling nanodevices that move and change shape on demand

BOSTON, Mass. – By emulating nature's design principles, a team at Harvard's Wyss Institute for Biologically Inspired Engineering, Harvard Medical School and Dana-Farber Cancer Institute has created nanodevices made of DNA that self-assemble and can be programmed to move and change shape on demand. In contrast to existing nanotechnologies, these programmable nanodevices are highly suitable for medical applications because DNA is both biocompatible and biodegradable.

The work appears in the June 20 advance online Nature Nanotechnology.

Built at the scale of one billionth of a meter, each device is made of a circular, single-stranded DNA molecule that, once it has been mixed together with many short pieces of complementary DNA, self-assembles into a predetermined 3D structure. Double helices fold up into larger, rigid linear struts that connect by intervening single-stranded DNA.

A tensegrity built with wooden rods and string. A diagrammatic image of a tensegrity built with DNA struts (shown as colored ladders folded into rods) and DNA cable strands (shown as colored single lines). Light gray arrows show contractile forces exerted by the cable strands, while dark gray arrows show compressive forces along the struts. An electron micrograph of an actual nanoscale tensegrity built using the new DNA-based, self-assembling nanofabrication capabilities. Scale bars equal 20 nanometers (billionths of a meter). Images by Tim Liedl

These single strands of DNA pull the struts up into a 3D form—much like tethers pull tent poles up to form a tent. The structure's strength and stability result from the way it distributes and balances the counteracting forces of tension and compression. This architectural principle—known as tensegrity—has been the focus of artists and architects for many years, but it also exists throughout nature. In the human body, for example, bones serve as compression struts, with muscles, tendons and ligaments acting as tension bearers that enable us to stand up against gravity. The same principle governs how cells control their shape at the microscale. "This new self-assembly based nanofabrication technology could lead to nanoscale medical devices and drug delivery systems, such as virus mimics that introduce drugs directly into diseased cells," said co-investigator and Wyss Institute director Don Ingber. A nanodevice that can spring open in response to a chemical or mechanical signal could ensure that drugs not only arrive at the intended target but are also released when and where desired. Further, nanoscopic tensegrity devices could one day reprogram human stem cells to regenerate injured organs. Stem cells respond differently depending on the forces around them. For instance, a stiff extracellular matrix—the biological glue surrounding cells—fabricated to mimic the consistency of bone signals stem cells to become bone, while a soupy matrix closer to the consistency of brain tissue signals the growth of neurons. Tensegrity nanodevices "might help us to tune and change the stiffness of extracellular matrices in tissue engineering someday," said first author Tim Liedl, who is now a professor at Ludwig-Maximilians-Universität in Munich. "These little Swiss Army knives can help us make all kinds of things that could be useful for advanced drug delivery and regenerative medicine," said lead investigator William Shih, Wyss core faculty member and associate professor of biological chemistry and molecular pharmacology at HMS and Dana-Farber Cancer Institute. "We also have a handy biological DNA Xerox machine that nature evolved for us," making these devices easy to manufacture. This new capability "is a welcome element in the structural DNA nanotechnology toolbox," said Ned Seeman, professor of chemistry at New York University. ### This research was funded by the Wyss Institute for Biologically Inspired Engineering at Harvard University, National Institutes of Health, Deutscher Akademischer Austauschdienst Fellowship, Swedish Science Council Fellowship and Claudia Adams Barr Program Investigator award. Written by Elizabeth Dougherty CITATION: Nature Nanotechnology, online publication, June 20, 2010 “Self-assembly of 3D prestressed tensegrity structures from DNA” Tim Liedl, Bjorn Hogberg, Jessica Tytell, Donald E. Ingber, William M. Shih WYSS INSTITUTE CONTACT: Mary Tolikas mary.tolikas@wyss.harvard.edu 617-432-7733 DANA-FARBER CANCER INSTITUTE CONTACT Bill Schaller william_schaller@dfci.harvard.edu 617-632-5357

The Wyss Institute for Biologically Inspired Engineering at Harvard University uses nature’s design principles to create breakthrough technologies that will revolutionize medicine, industry and the environment. Working as an alliance among Harvard’s Medical School, School of Engineering and Applied Sciences, and Faculty of Arts and Sciences, and in partnership with Beth Israel Deaconess Medical Center, Children’s Hospital Boston, Dana-Farber Cancer Institute, University of Massachusetts Medical School and Boston University, the Institute crosses disciplinary and institutional barriers to engage in high-risk, fundamental research that leads to transformative change. By applying biological principles, Wyss researchers are developing innovative new engineering solutions for healthcare, manufacturing, robotics, energy and sustainable architecture. These technologies are translated into commercial products and therapies through collaborations with clinical investigators, corporate alliances and new startups.

Harvard Medical School has more than 7,500 full-time faculty working in 11 academic departments located at the School's Boston campus or in one of 47 hospital-based clinical departments at 17 Harvard-affiliated teaching hospitals and research institutes. Those affiliates include Beth Israel Deaconess Medical Center, Brigham and Women's Hospital, Cambridge Health Alliance, Children's Hospital Boston, Dana-Farber Cancer Institute, Forsyth Institute, Harvard Pilgrim Health Care, Hebrew SeniorLife, Joslin Diabetes Center, Judge Baker Children's Center, Massachusetts Eye and Ear Infirmary, Massachusetts General Hospital, McLean Hospital, Mount Auburn Hospital, Schepens Eye Research Institute, Spaulding Rehabilitation Hospital, and VA Boston Healthcare System.

Contact: David Cameron david_cameron@hms.harvard.edu 617-432-0441 Harvard Medical School