Programmable Multivalent DNA-Origami Tension Probes for Reporting Cellular Traction Forces

• Type of Material: Article
• Authors: Palash K. Dutta, Georgia Institute of Technology; Yun Zhang, Emory University; Aaron Blanchard, Georgia Institute of Technology; Chenghao Ge, Georgia Institute of Technology; Muaz Rushdi, Georgia Institute of Technology; Kristin Weiss, Georgia Institute of Technology; Cheng Zhu, Emory University; Yonggang Ke, Emory University; Khalid Salaita, Emory University
• Language: English
• Date: 2018-08-01
• Publisher: American Chemical Society
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: Copyright © 2018 American Chemical Society
• Final Published Version (URL): http://dx.doi.org/10.1021/acs.nanolett.8b01374
• Title of Journal or Parent Work: Nano Letters
• ISSN: 1530-6984
• Volume: 18
• Issue: 8
• Start Page: 4803
• End Page: 4811
• Grant/Funding Information: The work was supported through NIGMS R01 GM124472 (K.S.); NSF 1350829 (K.S.); NSF IDBR 1353939 (K.S.); NIAID R21 AI135753 (Y.K. and C.Z.).
• Keywords: NANOSTRUCTURES; biomembrane force probe; Technology; platelets; SENSORS; Chemistry, Physical; NANOPARTICLES; Materials Science, Multidisciplinary; Nanoscience & Nanotechnology; SPECTROSCOPY; Science & Technology - Other Topics; BINDING; Physics; Chemistry, Multidisciplinary; SURFACE; Chemistry; cellular traction forces; Materials Science; PICONEWTON FORCES; ARCHITECTURE; Physical Sciences; Science & Technology; NANOSCALE; Physics, Condensed Matter; Physics, Applied; ADHESIONS; DNA origami
• Research Categories: Chemistry, Physical; Engineering, Biomedical

Abstract

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.