%0 Online Multimedia %A Dutta, Palash K. %A Zhang, Yun %A Blanchard, Aaron T. %A Ge, Chenghao %A Rushdi, Muaz %A Weiss, Kristin %A Zhu, Cheng %A Ke, Yonggang %A Salaita, Khalid %D 2018 %T Programmable Multivalent DNA-Origami Tension Probes for Reporting Cellular Traction Forces %U https://acs.figshare.com/articles/media/Programmable_Multivalent_DNA-Origami_Tension_Probes_for_Reporting_Cellular_Traction_Forces/6743441 %R 10.1021/acs.nanolett.8b01374.s003 %2 https://acs.figshare.com/ndownloader/files/12302486 %K tailorable number %K DNA origami tension sensor %K Reporting Cellular Traction Forces Mechanical forces %K protein assemblies %K DOTP-functionalized surfaces increases %K Programmable Multivalent DNA-Origami Tension Probes %K DOTP library %K single-molecule force spectroscopy %K blood platelets %K six-helix-bundle DNA-origami tension probes %K tension signal %K nanoscale organization %K tension-reporting hairpins %K nanometer-length scale %K tunable tension response threshold %K tunable number %K novel library %K force-sensing probes %K force generation %K cell-receptor ligands %K ligand density %K cell development %X Mechanical forces are central to most, if not all, biological processes, including cell development, immune recognition, and metastasis. Because the cellular machinery mediating mechano-sensing and force generation is dependent on the nanoscale organization and geometry of protein assemblies, a current need in the field is the development of force-sensing probes that can be customized at the nanometer-length scale. In this work, we describe a DNA origami tension sensor that maps the piconewton (pN) forces generated by living cells. As a proof-of-concept, we engineered a novel library of six-helix-bundle DNA-origami tension probes (DOTPs) with a tailorable number of tension-reporting hairpins (each with their own tunable tension response threshold) and a tunable number of cell-receptor ligands. We used single-molecule force spectroscopy to determine the probes’ tension response thresholds and used computational modeling to show that hairpin unfolding is semi-cooperative and orientation-dependent. Finally, we use our DOTP library to map the forces applied by human blood platelets during initial adhesion and activation. We find that the total tension signal exhibited by platelets on DOTP-functionalized surfaces increases with the number of ligands per DOTP, likely due to increased total ligand density, and decreases exponentially with the DOTP’s force-response threshold. This work opens the door to applications for understanding and regulating biophysical processes involving cooperativity and multivalency. %I ACS Publications