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Review Article

Kinesin and Dynein Mechanics: Measurement Methods and Research Applications

[+] Author and Article Information
Zachary Abraham, Daniel Hayosh

Department of Mechanical and
Aerospace Engineering,
Case Western Reserve University,
Cleveland, OH 44106

Emma Hawley

Department of Biomedical Engineering,
Case Western Reserve University,
Cleveland, OH 44106

Victoria A. Webster-Wood

Mem. ASME
Department of Mechanical and
Aerospace Engineering,
Case Western Reserve University,
10900 Euclid Avenue,
Cleveland, OH 44106
e-mail: Webster-wood@case.edu

Ozan Akkus

Mem. ASME
Department of Mechanical and
Aerospace Engineering,
Case Western Reserve University,
Cleveland, OH 44106

1Corresponding author.

Manuscript received July 2, 2017; final manuscript received September 7, 2017; published online January 12, 2018. Editor: Victor H. Barocas.

J Biomech Eng 140(2), 020805 (Jan 12, 2018) (11 pages) Paper No: BIO-17-1289; doi: 10.1115/1.4037886 History: Received July 02, 2017; Revised September 07, 2017

Motor proteins play critical roles in the normal function of cells and proper development of organisms. Among motor proteins, failings in the normal function of two types of proteins, kinesin and dynein, have been shown to lead many pathologies, including neurodegenerative diseases and cancers. As such, it is critical to researchers to understand the underlying mechanics and behaviors of these proteins, not only to shed light on how failures may lead to disease, but also to guide research toward novel treatment and nano-engineering solutions. To this end, many experimental techniques have been developed to measure the force and motility capabilities of these proteins. This review will (a) discuss such techniques, specifically microscopy, atomic force microscopy (AFM), optical trapping, and magnetic tweezers, and (b) the resulting nanomechanical properties of motor protein functions such as stalling force, velocity, and dependence on adenosine triphosophate (ATP) concentrations will be comparatively discussed. Additionally, this review will highlight the clinical importance of these proteins. Furthermore, as the understanding of the structure and function of motor proteins improves, novel applications are emerging in the field. Specifically, researchers have begun to modify the structure of existing proteins, thereby engineering novel elements to alter and improve native motor protein function, or even allow the motor proteins to perform entirely new tasks as parts of nanomachines. Kinesin and dynein are vital elements for the proper function of cells. While many exciting experiments have shed light on their function, mechanics, and applications, additional research is needed to completely understand their behavior.

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Figures

Grahic Jump Location
Fig. 1

The directional stepping process of kinesin (left) and dynein (right)

Grahic Jump Location
Fig. 2

A comparison of the structure of dynein and kinesin. The left-side image, modified from Ref. [7], depicts dynein next to the globular motor domain that is consistent between all kinesins. The binding of dynein is modulated during the ATPase cycle via primarily the AAA1 domain. On the right side is a detailed view of the kinesin motor domain (image from public domain).

Grahic Jump Location
Fig. 3

(a) A diagram of the optical trapping measurement technique. A bead is captured by the focused optical trap such that either a force is applied, or the escape force (Fk) generated by the protein to move the bead within the trap are met with a resistive force (Ft). (b) The motion of the bead can be tacked with DIC (as shown, image from Ref. [14], CC BY 3.0) or with fluorescent microscopy and related to the applied force.

Grahic Jump Location
Fig. 4

Using AFM, the position of kinesin on a microtubule can be visualized in three-dimensional. This functions for high concentrations of motor proteins (a) or for single proteins (b). Image from Ref. [31].

Grahic Jump Location
Fig. 5

(a) Magnetic tweezers, similar to optical traps, trap a bead which is attached to either a motor protein or a microtubule. An external force (Fm) can then be applied to the bead via a magnetic field. The effect of the force on the bead can be seen between (b) when no magnetic field is present and (c) when the field is applied. (b) and (c) adapted from Ref. [28].

Grahic Jump Location
Fig. 6

(a) The relationship between ATP concentration and kinesin velocity as reported across the literature (see Table 1). (b) The effect of temperature on kinesin velocity at two ATP concentrations [34,43]. At both concentrations, the relationship is seen to follow a similar trend. (c) Approximate force–velocity relationships adapted from the existing literature [9,12,18,50].

Grahic Jump Location
Fig. 7

Engineered motor proteins offer exciting new possibilities in research and clinical applications. By modifying an existing motor protein, researchers can generate new structures capable of performing novel tasks or improving native protein function.

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