DNA tensiometer reveals catch-bond detachment kinetics of kinesin-1, -2, and -3
5 affiliations
- 1Department of Biomedical Engineering, Pennsylvania State University, University Park, Pennsylvania, USA
- 2Pennsylvania State University
- 3Department of Mathematics, Tulane University, New Orleans, Louisiana, USA
- 4Tulane University
- 5Department of Chemistry, Pennsylvania State University, University Park, Pennsylvania, USA
Abstract
Bidirectional cargo transport by kinesin and dynein is essential for cell viability and defects are linked to neurodegenerative diseases. Computational modeling suggests that the load-dependent off-rate is the strongest determinant of which motor 'wins' a kinesin-dynein tug-of-war, and optical tweezer experiments find family-dependent differences in the sensitivity of detachment to load, with kinesin-3 > kinesin-2 > kinesin-1. However, in reconstituted kinesin-dynein pairs vitro, all three kinesin families compete nearly equally well against dynein. Modeling and experiments have confirmed that vertical forces inherent to the large trapping beads enhance kinesin-1 dissociation rates. In vivo, vertical forces are expected to range from negligible to dominant, depending on cargo and microtubule geometries. To investigate the detachment and reattachment kinetics of kinesin-1, 2 and 3 motors against loads oriented parallel to the microtubule, we created a DNA tensiometer comprising a DNA entropic spring attached to the microtubule on one end and a motor on the other. Kinesin dissociation rates at stall were slower than detachment rates during unloaded runs, and the complex reattachment kinetics were consistent with a weakly-bound 'slip' state preceding detachment. Kinesin-3 behaviors under load suggested that long KIF1A run lengths result from the concatenation of multiple short runs connected by diffusive episodes. Stochastic simulations were able to recapitulate the load-dependent detachment and reattachment kinetics for all three motors and provide direct comparison of key transition rates between families. These results provide insight into how kinesin-1, -2 and -3 families transport cargo in complex cellular geometries and compete against dynein during bidirectional transport.
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BibTeX
@article{noell2026tensiometer,
title = {{DNA tensiometer reveals catch-bond detachment kinetics of kinesin-1, -2, and -3}},
author = {Crystal R. Noell and Tzu-Chen Ma and Rui Jiang and Scott A. McKinley and William Olaf Hancock},
journal = {eLife},
year = {2026},
month = jul,
doi = {10.7554/elife.108837.4},
url = {https://doi.org/10.7554/elife.108837.4},
note = {CC BY},
}
RIS
TY - JOUR
TI - DNA tensiometer reveals catch-bond detachment kinetics of kinesin-1, -2, and -3
AU - Crystal R. Noell
AU - Tzu-Chen Ma
AU - Rui Jiang
AU - Scott A. McKinley
AU - William Olaf Hancock
PY - 2026
DA - 2026/07/20
JO - eLife
DO - 10.7554/elife.108837.4
UR - https://doi.org/10.7554/elife.108837.4
AB - Bidirectional cargo transport by kinesin and dynein is essential for cell viability and defects are linked to neurodegenerative diseases. Computational modeling suggests that the load-dependent off-rate is the strongest determinant of which motor 'wins' a kinesin-dynein tug-of-war, and optical tweezer experiments find family-dependent differences in the sensitivity of detachment to load, with kinesin-3 > kinesin-2 > kinesin-1. However, in reconstituted kinesin-dynein pairs vitro, all three kinesin families compete nearly equally well against dynein. Modeling and experiments have confirmed that vertical forces inherent to the large trapping beads enhance kinesin-1 dissociation rates. In vivo, vertical forces are expected to range from negligible to dominant, depending on cargo and microtubule geometries. To investigate the detachment and reattachment kinetics of kinesin-1, 2 and 3 motors against loads oriented parallel to the microtubule, we created a DNA tensiometer comprising a DNA entropic spring attached to the microtubule on one end and a motor on the other. Kinesin dissociation rates at stall were slower than detachment rates during unloaded runs, and the complex reattachment kinetics were consistent with a weakly-bound 'slip' state preceding detachment. Kinesin-3 behaviors under load suggested that long KIF1A run lengths result from the concatenation of multiple short runs connected by diffusive episodes. Stochastic simulations were able to recapitulate the load-dependent detachment and reattachment kinetics for all three motors and provide direct comparison of key transition rates between families. These results provide insight into how kinesin-1, -2 and -3 families transport cargo in complex cellular geometries and compete against dynein during bidirectional transport.
SN - 2050-084X
ER -