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Engineering an artificial catch bond using mechanical anisotropy.

Zhaowei Liu1,2,3, Haipei Liu1,2, Andrés M Vera4

  • 1Institute of Physical Chemistry, Department of Chemistry, University of Basel, 4058, Basel, Switzerland.

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|April 8, 2024
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Summary
This summary is machine-generated.

Researchers engineered artificial catch bonds by modifying anchor geometry in the Dockerin G:Cohesin E complex. This modification increases bond lifetime under force, a rare property with potential applications in biomaterials and understanding cellular mechanics.

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Area of Science:

  • Biophysics
  • Protein Engineering
  • Molecular Mechanics

Background:

  • Catch bonds are rare protein-protein interactions that strengthen under force.
  • The Dockerin G:Cohesin E (DocG:CohE) complex is a mechanostable adhesion complex found in bacteria.
  • Understanding and engineering catch bonds can lead to novel biomaterials and insights into cellular processes.

Purpose of the Study:

  • To engineer artificial catch bonding behavior in the DocG:CohE complex.
  • To investigate the role of anchor geometry in determining catch or slip bond behavior.
  • To explore the mechanical properties and unbinding pathways of the modified complex.

Main Methods:

  • Atomic Force Microscopy (AFM) single-molecule force spectroscopy was used to mechanically probe the DocG:CohE complex.
  • Bioorthogonal click chemistry enabled precise control over five different anchor geometries for force application.
  • Kinetic Monte Carlo simulations and single-molecule Förster Resonance Energy Transfer (smFRET) were employed to analyze rupture dynamics and binding modes.

Main Results:

  • Modifying the anchor geometry, specifically pulling between residue #13 on CohE and the N-terminus of DocG, induced catch bond behavior.
  • In contrast, native and other tested pulling geometries resulted in slip bond behavior.
  • Simulations showed strong agreement with experimental rupture force and lifetime distributions, and smFRET confirmed force-dependent unbinding pathways.

Conclusions:

  • Anchor point selection and mechanical anisotropy are critical factors in engineering artificial catch bonds.
  • The study demonstrates a method to create tunable catch bonds using a naturally occurring protein complex.
  • These findings have implications for designing force-responsive biomaterials and understanding mechanobiology.