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Isometric and Eccentric Force Generation Assessment of Skeletal Muscles Isolated from Murine Models of Muscular Dystrophies
Published on: January 31, 2013
Dynein arms are strain-dependent direction-switching force generators.
Chikako Shingyoji1, Izumi Nakano1, Yuichi Inoue1
1Department of Biological Sciences, The University of Tokyo, Hongo, Tokyo, Japan.
Axonemal dynein motors can generate force in both forward and backward directions along microtubules. Mechanical strain is crucial for switching this force generation directionality, revealing unique motor behavior.
Area of Science:
- Molecular Motor Dynamics
- Cellular Mechanics
- Biophysics
Background:
- Dynein motors are crucial for intracellular transport, typically moving towards the minus end of microtubules.
- Previous studies indicated oscillatory or bidirectional force generation in dyneins under specific conditions.
- The response of axonemal dynein to mechanical forces and its capacity for directional switching remained largely unexplored.
Purpose of the Study:
- To investigate whether axonemal dynein can switch its force generation direction.
- To characterize the force-generating capabilities of axonemal dynein under varying mechanical conditions.
- To understand the role of external forces in modulating dynein's directional movement.
Main Methods:
- Utilized optical trap techniques to measure force generation by dynein.
- Employed UV-photolysis of caged ATP to control motor activity.
- Studied both isolated dynein and dynein arms attached to doublet microtubules.
Main Results:
- Observed that axonemal dynein can repeatedly generate force in both forward (5-6 pN) and backward (∼4 pN) directions along microtubules.
- Demonstrated bidirectional force generation in both isolated dynein and dynein arms attached to native structures.
- Showed that applying a plus-end directed external force before ATP application can stimulate backward force generation.
Conclusions:
- Axonemal dynein exhibits unique, multi-modal force generation, including bidirectional and oscillatory capabilities.
- Mechanical strain plays a significant role in switching the directionality of force generation in axonemal dyneins.
- These findings expand our understanding of motor protein mechanics and regulation.
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