Effect of catch bonding on transport of cellular cargo by dynein motors

Anil Nair, Sameep Chandel, Mithun K. Mitra, Sudipto Muhuri, and Abhishek Chaudhuri

Phys. Rev. E 94, 032403 – Published 2 September 2016

Abstract

Recent experiments have demonstrated that dynein motors exhibit catch bonding behavior, in which the unbinding rate of a single dynein decreases with increasing force, for a certain range of force. Motivated by these experiments, we study the effect of catch bonding on unidirectional transport properties of cellular cargo carried by multiple dynein motors. We introduce a threshold force bond deformation (TFBD) model, consistent with the experiments, wherein catch bonding sets in beyond a critical applied load force. We find catch bonding can result in dramatic changes in the transport properties, which are in sharp contrast to kinesin-driven unidirectional transport, where catch bonding is absent. We predict that under certain conditions, the average velocity of the cellular cargo can actually increase as applied load is increased. We characterize the transport properties in terms of a velocity profile plot in the parameter space of the catch bond strength and the stall force of the motor. This plot yields predictions that may be experimentally accessed by suitable modifications of motor transport and binding properties.

Received 16 February 2016

DOI:https://doi.org/10.1103/PhysRevE.94.032403

Physics Subject Headings (PhySH)

Intracellular transport Subcellular processes & properties

Physics of Living Systems

Authors & Affiliations

Anil Nair¹, Sameep Chandel², Mithun K. Mitra³, Sudipto Muhuri¹, and Abhishek Chaudhuri²

¹Department of Physics, Savitribai Phule Pune University, Ganeshkhind, Pune 411007, India
²Indian Institute of Science Education and Research Mohali, Knowledge City, Punjab 140306, India
³Department of Physics, IIT Bombay, India

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Vol. 94, Iss. 3 — September 2016

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Images

Figure 1
Schematic representation of dynein walking on a MT filament, and catch bonding under applied load. The magnified region shows the MT binding domain of the dynein stalk, which can undergo a conformational change under applied load.
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Figure 2
(a) Variation of unbinding rate of a single dynein with constant load force ( $F$ ): The red line corresponds to experiments from Ref. [17]. The dashed curve is obtained from the TFBD model with $α = 68$ , $f_{o} = 40.7$ pN, $f_{m} = 1.4$ pN, $f_{d} = 0.67$ pN, $f_{s} = 1.25$ pN [17], and $ɛ_{0} = 1$ $s^{- 1}$ [17]. Transport properties of cargo carried by five dyneins as functions of F: (b) effective unbinding rate K vs $F$ ; (c) average number of attached motors vs F; and (d) average velocity vs F. For (b)–(d), the parameter values chosen are the same as in (a) with $π_{ad} = 1.6$ $s^{- 1}$ [9] and $v_{o} = 0.65$ $μ m / s$ [9].
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Figure 3
Probability distribution for the number of bound motors in a system with $N = 5$ for the (a) TFBD and (b) BD models. Compared to the zero-force case (green crosses), where the probability distribution is peaked at zero bound motors and then decreases monotonically, for finite forces, both models show a nonmonotonic probability distribution, with the distribution peaking at larger $k$ in the BD case. Panels (c) and (d) show the effective unbinding rate and the average number of bound motors as a function of force for a slip bond (solid blue line), as opposed to the TFBD (green dashed curve) and the BD (red dotted line) models. Data are for $α = 20$ and $f_{s} = 2$ pN with $v_{0} = 0.65$ $μ m / s$ [9], $ɛ_{0} = 1.0$ $s^{- 1}$ [17], $f_{0} = 7$ pN, $f_{m} = 1.4$ pN, $f_{d} = 0.67$ pN, and $π_{ad} = 0.1$ $s^{- 1}$ .
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Figure 4
Force-velocity curves: (a) TFBD model for two different binding rates, $π_{ad} = 0.1$ $s^{- 1}$ (solid blue curve) and $π_{ad} = 1.0$ $s^{- 1}$ (dashed red curve). The solid curve shows four velocity humps which reduces to a single-hump velocity profile on increasing $π_{ad}$ . (b) BD model for $π_{ad} = 0.01$ $s^{- 1}$ (solid blue curve) and $π_{ad} = 0.1$ $s^{- 1}$ (dashed red curve). In this case, a four-hump profile reduces to a monotonically decreasing velocity profile on increasing $π_{ad}$ . Data are for $N = 5$ motors with $v_{0} = 0.65$ $μ m / s$ [9], $ε_{0} = 1.0$ $s^{- 1}$ [17], $α = 35$ , and $f_{0} = 7$ , $f_{m} = 1.4$ , $f_{d} = 0.67$ , and $f_{s} = 2$ pN.
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Figure 5
Velocity diagrams in the $α − F_{s}$ plane for the TFBD model with $π_{ad} =$ (a) 0.1 and (b) 1.0 $s^{- 1}$ , and for the BD model with $π_{ad} =$ (a) 0.01 and (b) 0.1 $s^{- 1}$ . The violet region corresponds to a monotonically decreasing force-velocity profile. The red, green, blue, and yellow regions correspond to velocity profiles with one, two, three, and four humps, respectively (see Fig. 4 for examples of individual velocity profiles). Parameter values are the same as in Fig. 4. Stall forces are in pN.
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