Nano@Tech Virtual:DNA Mechanotechnology: Repurposing Nucleic Acids as Force Sensors, Actuators, and Motors
Khalid Salaita - Professor
Department of Chemistry, Emory University
Abstract: Under a microscope, cells appear stationary, but in reality, cells are highly dynamic structures that are pulling and pushing on one another and on their surroundings. These pulls and pushes are mediated by minuscule forces – at the scale of tens of piconewtons, less than one-billionth the weight of an apple. For context, a force of 7 pN applied a distance of 1 nm equals 1 kcal/mol. Nonetheless, these forces can have profound biochemical impact. For example, the rapidly fluctuating forces in a growing embryo alter cell growth and fate by activating different adhesion pathways. Despite the importance of mechanics in most life processes there are limited methods to study and manipulate forces at molecular scales. In this talk, I will describe the development of DNA mechanotechnology - nucleic acid nanostructures that can sense, generate and transmit piconewton forces. I’ll start by describing molecular tension probes which are DNA structures that unfold at specific thresholds of tension. I will show exciting new advances that harness fluorescence polarization spectroscopy and super-resolution imaging to provide the highest resolution maps of cell traction forces reported to date. Armed with these new tools, I will demonstrate that molecular forces not only give rise to tissue architecture but also to boost the fidelity of information transfer between cells. We dubbed this mechanism mechanical proofreading in analogy to the kinetic proofreading model used explain the extraordinary fidelity of DNA replication and protein expression. Next, I will describe DNA nanostructures that transmit forces and drive mechanical unfolding of target molecules. With these actuators we show the first example of a force-pump probe type of experiment to perform time-resolved unfolding of biomolecules. Finally, I will end with a brief description of DNA motors that open the door for next generation point of care sensing technologies.
Bio: Khalid Salaita is a Professor of Chemistry at Emory University. Khalid pursued undergraduate studies at Old Dominion University under the mentorship of Prof. Nancy Xu studying the spectroscopic properties of plasmonic nanoparticles. He obtained his Ph.D. with Prof. Chad Mirkin at Northwestern University studying the electrochemical properties of organic adsorbates patterned onto gold films and developed massively parallel scanning probe lithography approaches. From 2006-2009, Khalid was a postdoctoral scholar with Prof. Jay T. Groves at the University of California at Berkeley where he investigated the role of receptor clustering in modulating cell signaling. In 2009, Khalid started his own lab at Emory University, where he investigates the interface between living systems and engineered nanoscale materials. To achieve this goal, his group has pioneered the development of molecular force sensor, DNA mechanotechnology, smart therapeutics, and nanoscale mechanical actuators to manipulate living cells. In recognition of his independent work, Khalid has received a number of awards, most notably the Alfred P. Sloan Research Fellowship, the Camille-Dreyfus Teacher Scholar award, the National Science Foundation Early CAREER award, and the Kavli Fellowship. Khalid is currently a member of the Enabling Bioanalytical and Imaging Technologies (EBIT) NIH study Section and an Associate Editor of Smart Materials. Khalid’s program has been supported by NSF, NIH, and DARPA.
Co-sponsored by Microphysiological Systems Seminar Series