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Mol Biol Cell. 2018 Oct 3:mbcE18010022. doi: 10.1091/mbc.E18-01-0022. [Epub ahead of print]

Application of the fluctuation theorem for non-invasive force measurement in living neuronal axons.

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Department of Applied Physics, Graduate School of Engineering, Tohoku University, Sendai, Japan.
Laboratory for Cell Polarity Regulation, Center for Biosystems Dynamics Research (BDR), RIKEN, Osaka, Japan.
Graduate School of Frontier Biosciences, Osaka University, Osaka, Japan.
Laboratory for Cell Dynamics Observation, Center for Biosystems Dynamics Research (BDR), RIKEN, Osaka, Japan.
Department of Physics, Universal Biology Institute (UBI), and the International Research Center for Neurointelligence (WPI-IRCN), The University of Tokyo, Tokyo, Japan.


Although its importance is recently widely accepted, force measurement has been difficult in living biological systems, mainly due to the lack of the versatile non-invasive force measurement methods. The fluctuation theorem, which represents the thermodynamic properties of small fluctuating non-equilibrium systems, has been applied to the analysis of the thermodynamic properties of motor proteins in vitro. Here, we extend it to the axonal transport (displacement) of endosomes. The distribution of the displacement fluctuation had three or four distinct peaks around multiples of a unit value, which the fluctuation theorem can convert into the drag force exerted on the endosomes. The results demonstrated that a single cargo vesicle is conveyed by one to three or four units of force production.

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