About this item:

211 Views | 154 Downloads

Author Notes:

Khalid Salaita: k.salaita@emory.edu

Yonggang Ke: yonggang.ke@emory.edu.

The authors thank M. Bathe and K. Pan (Massachusetts Institute of Technology) for their assistance with setting up finite element simulations; and W. Lam and Y. Qiu (Georgia Institute of Technology and Emory University) for assistance with obtaining human platelets.

The authors declare no competing financial interest.

Subjects:

Research Funding:

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:

  • Science & Technology
  • Physical Sciences
  • Technology
  • Chemistry, Multidisciplinary
  • Chemistry, Physical
  • Nanoscience & Nanotechnology
  • Materials Science, Multidisciplinary
  • Physics, Applied
  • Physics, Condensed Matter
  • Chemistry
  • Science & Technology - Other Topics
  • Materials Science
  • Physics
  • DNA origami
  • cellular traction forces
  • platelets
  • biomembrane force probe
  • PICONEWTON FORCES
  • NANOSTRUCTURES
  • SPECTROSCOPY
  • NANOSCALE
  • ADHESIONS
  • SENSORS
  • BINDING
  • SURFACE
  • NANOPARTICLES
  • ARCHITECTURE

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

Journal Title:

Nano Letters

Volume:

Volume 18, Number 8

Publisher:

, Pages 4803-4811

Type of Work:

Article | Post-print: After Peer Review

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.

Copyright information:

Copyright © 2018 American Chemical Society

Export to EndNote