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

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  • 1Department of Chemistry , Emory University , 1515 Dickey Drive , Atlanta , Georgia 30322 , United States.

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|June 19, 2018
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Summary

Researchers developed customizable DNA origami tension probes (DOTPs) to measure piconewton forces from living cells. These probes reveal how platelet forces change with ligand number and sensor thresholds, advancing mechanobiology.

Keywords:
DNA origamibiomembrane force probecellular traction forcesplatelets

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Area of Science:

  • Biophysics
  • Molecular Biology
  • Nanotechnology

Background:

  • Mechanical forces are crucial for cellular processes like development and metastasis.
  • Understanding cellular force generation requires nanoscale force-sensing tools.
  • Existing methods lack the nanometer-scale customization needed for precise force mapping.

Purpose of the Study:

  • To engineer and validate DNA origami tension probes (DOTPs) for measuring piconewton forces from living cells.
  • To create a library of DOTPs with tunable parameters like ligand number and force-response thresholds.
  • To map cellular forces, specifically those exerted by human blood platelets during adhesion and activation.

Main Methods:

  • Designed and synthesized a library of six-helix-bundle DNA origami tension probes (DOTPs).
  • Utilized single-molecule force spectroscopy to characterize probe tension response thresholds.
  • Employed computational modeling to analyze hairpin unfolding mechanics.
  • Applied DOTPs to quantify forces generated by human blood platelets.

Main Results:

  • DOTPs successfully mapped piconewton forces generated by living cells, specifically human blood platelets.
  • The total tension signal increased with the number of ligands per DOTP, indicating density effects.
  • Tension signals decreased exponentially with increasing DOTP force-response thresholds.
  • Hairpin unfolding within DOTPs was found to be semi-cooperative and orientation-dependent.

Conclusions:

  • The developed DOTP library offers a versatile platform for nanoscale force mapping in biological systems.
  • These probes enable the study of mechanosensing and force generation with tunable parameters.
  • The findings provide insights into platelet biomechanics and open avenues for regulating biophysical processes involving multivalency and cooperativity.