Abstract:
Modern machines, which are composed of force-generating motors, force sensors, and load-bearing structures, enabled the industrial revolution and are foundational to human civilization. Miniaturization to the nm scale would enable the manipulation of biomolecules for applications in medicine, biological research, and material development. Such machines are typically difficult to build because of their small size. However, the ability to modify and assemble nucleic acids combined with single molecule force spectroscopy studies have propelled the emergence of “DNA mechanotechnology” which is defined as nucleic acids engineered to generate, transmit, and sense mechanical forces at the nanoscale. DNA mechanotechnology is particularly well suited for measuring and controlling piconewton (pN)–scale forces. In this talk, I will describe our efforts aimed at the development of nucleic acid force sensors and motors. In the area of force sensors, I will show exciting new advances in DNA force sensors that harness fluorescence polarization spectroscopy and super-resolution imaging to provide the highest resolution maps of cell traction forces reported to date (1,2). 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. The second part of the talk will focus on DNA motors that consume chemical energy to produce mechanical work (3). In this part, I will demonstrate how this far-from equilibrium motor can offer exciting new opportunities for chemical sensing.
References:
- “Live-cell super-resolved PAINT imaging of piconewton cellular traction forces” Nature Methods, 2020
- "Mapping the 3D Orientation of Piconewton Integrin Traction Forces" Nature Methods, 2018.
- “High-speed DNA-based rolling motors powered by RNase H”, Nature Nanotechnology, 2016.
Bio:
Khalid Salaita is a Professor of Chemistry and Program Faculty of Biomedical Engineering at Emory University in Atlanta, Georgia (USA). Khalid grew up in Jordan and moved to the US in 1997 to pursue his undergraduate studies. He obtained his Ph.D. with Prof. Chad Mirkin at Northwestern University (Evanston, IL) in 2006. From 2006-2009, Khalid was a postdoctoral scholar with Prof. Jay T. Groves at the University of California at Berkeley (USA) where he investigated membrane biophysics. In 2009, Khalid started his own lab at Emory University, where he investigates the interface between living systems and engineered nanoscale materials. 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 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) study Section and an Associate Editor of Smart Materials.