The Molecular Motor

It is not common to use a gaseous poison like phosgene to fuel a motor, but it is a reality. Devised by Kelly at Boston in 1999, it led to the world s first molecular motor, 

sometimes called the Boston motor [306-309). It consists of just 78 atoms (320) and has a spindle of triptycene, which rotates about a carbon-carbon single bond as an axle between the triptycene and a helicene as a base plate. The triptycene can only rotate in a clockwise direction because the chiral helicene acts like a friction or back-pedaling brake shaped in an asymmetric skew. Chirality is the reason for the unidirectional rotation. 

Since phosgene enters into the motor as a high-energy molecule (320a — 321) and leaves it as the low-energy molecule CO2 (324 320b), it fulfils the characteristics 

Although this molecular motor does not achieve continuous and fast rotation, the design principles may prove relevant for a better understanding of biological molecular motors producing unidirectional rotary motion. 

A molecular motor with unidirectional rotation driven by visible light has been described [311]. Hereby the rotor is donor-acceptor substituted by dimethylamino-and nitro-groups. 

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The life cycle of these organelles, their kinetics and molecular cargo, the molecular motors driving their transport and the substrates along which these movements track constitute interrelated aspects of what is broadly termed axonal transport. A primary aim of this chapter is to provide an understanding of this form of intraneuronal traffic. Achieving this goal requires an appreciation of the dynamics and structure of the relevant neuronal components and structures. Studies of how cellular structures and components move from where they are synthesized to where they are utilized comprise an... 

Vale, R. D. The molecular motor toolbox for intracellular transport. Cell 112 467-480,2003. 

In nonequilibrium steady states, the mean currents crossing the system depend on the nonequilibrium constraints given by the affinities or thermodynamic forces which vanish at equihbrium. Accordingly, the mean currents can be expanded in powers of the affinities around the equilibrium state. Many nonequilibrium processes are in the linear regime studied since Onsager classical work [7]. However, chemical reactions are known to involve the nonlinear regime. This is also the case for nanosystems such as the molecular motors as recently shown [66]. In the nonlinear regime, the mean currents depend on powers of the affinities so that it is necessary to consider the full Taylor expansion of the currents on the affinities ... 

Any macroscopic motor is divided into a static portion, the stator, and a portion that is moving with respect to the static portion, called the rotor. To understand the mechanical properties of the molecular motor, we have to look at the properties of the motor s rotor and stator and their interactions on a molecular level. In the case of the A/V/F-ATPases, deciding which portion to call the rotor and which the stator is based on the relative molecular masses of the two functional elements. In the E. coli F-ATPase, for example, the stator is composed of with a relative molecular... 

An example of a nanodevice that might have important practical uses is the molecular motor, a device that will convert electrical, solar, chemical, or some other form of energy into mechanical energy. Many kinds of nanomotors occur in living organisms, hut so far relatively little progress has been made in the development of synthetic analogs of such devices. 

The determination of the structures of the molecular motor proteins myosin and kinesin first revealed the evolutionary connections on which Chapter 34, on molecular motors, is based. 

The horse, like all animals, is powered by the molecular motor protein, myosin. A portion of myosin moves dramatically (as shown above) in response to ATP binding, hydrolysis, and release, propelling myosin along an actin filament. This molecular movement is translated into movement of the entire animal, excitingly depicted in da Vinci s rearing horse. [(Left) Leonardo da Vinci s "Study of a rearing horse" for the battle of Anghiari (c. 1504) from The Royal Collection Her Royal Majesty Queen Elizabeth II.]... 

Our recent neuronal imaging in transgenic mice has yielded an unexpectedly important discovery [38]. We found that Second Harmonic Generation (SHG) imaging of neurons by SHG radiation by the microtubule assemblies in dendrites showed parallel polarity orientation in the microtubule orientations in dendrites. Microtubule polarity dictates the selective directions of motion of the molecular motors on microtubules serving as the neuron s messengers... 

Figure 34.1 Motion within cells. This high-voltage electron micrograph shows the mitotic apparatus in a metaphase mammalian cell. The targe cylindrical objects are chromosomes, and the threadlike structures stretched across the center are microtubules—tracks for the molecular motors that move chromosomes. Many processes, including chromosome segregation in mitosis, depend on the action of molecular-motor proteins.. [Courtesy of Dr. J. R. McIntosh.]...

Scheme 9 provides (using 47 for purposes of illustration) molecular detail for the concepts outlined in Fig. 21. In essence, the proof of principle for the molecular motor starts with 47a. Compound 47a is one of three low-energy rotational isomers (rotamers) about the axle connecting the triptycene and helicene components (47b is a second low-energy rotamer). Rotamer 47a is activated by reaction with phosgene to give the isocyanate 49. Isocyanate 49 is chemically armed to react with the OH group in the hydroxypropyl tether attached to the helicene, but, in the rotational ground state 49, the isocyanate...

Differentiation of the ookinete involves three key processes (1) a change in the surface from a fertilization-receptive macrogamete into an invasive cell capable of resisting immune attack by the mosquito and interaction with the mosquito mid-gut, (2) fabrication of a cortex and apical complex that contain the molecular motor and secretory apparatus to escape the bloodmeal and invade the mid-gut wall and (3) meiosis... 

Fig. 2.12. Peclet number as a function of driving frequency (top, solid line) for the molecular motor with a harmonically modulated fuel concentration (bottom right). The stroke time was chosen to be distributed according to a F-density eq. (2.43) with n = 100. The fastest excitation time 7([X]max) is 20 times smaller than the mean stroke time T while the slowest excitation time 7([-X]min) is 5 times larger than the mean stroke time T. The dashed and dotted lines in the top plot show the Peclet number for a constant excitation rate 7([2f]max) and 7([X]nim) respectively. [15]...

In this chapter we will describe the general features of the molecule that is the molecular motor of vertebrate smooth muscle cells. As shown in Fig. 1, this myosin molecule is composed of two heavy chains of approximately 220 kDa each and two pairs of light chains that are located in the neck region, just carboxyl-terminal to the globular myosin head domain. The properties and structure of the myosin light chains are covered in Chapter 2 of this volume. 

The 20-amino acid residue peptide RS-20, whose sequence derives from smooth muscle myosin light chain kinase (MLCK), is a well-known calmodulin binding peptide [144], Both, RS-20 and LMS-1, a 13-residue peptide derived from the autoinhibitory domain of MLCK, have the capability of inhibiting MLCK phosphorylation activity, normally directed toward the molecular motor, actin binding protein myosin II, which is involved in physiological phenomena like cell polarization and locomotion [145, 146]. 

Here we derive a model for the collective spatio-temporal dynamics of microtubules starting with a master equation for interacting inelastic polar rods [13]. Our model differs from the transport equations [12] in that it maintains the detailed balance of rods with a certain orientation. The model exhibits an onset of orientational order for large enough density of microtubules and molecular motors, formation of vortices and then asters with the increase in the molecular motor concentration, in a qualitative agreement with experiment. 

Molecular motors enter the model implicitly by specifying the interaction rules between two rods. Since the diffusivity of molecular motors is about 100 times larger than that of microtubules, as a first approximation we neglect spatial variations of the molecular motor density. While the varying concentration of molecular motors affects certain quantitative aspects [7], our analysis captures salient features of the phenomena and the collision rules are spatially homogeneous. All rods are assumed to be of equal length I and diameter d I,... 

Hoiczyk, E. and Baumeister, W. (1998). The junctional pore complex, a prokaryotic secretion organelle, is the molecular motor underlying gliding motility in cyanobacteria. Curr. Biol. 8, 1161-1168. 

It is clear that there is enormous complexity within each ctenophore plate it would be a herculean task to reproduce the molecular motor of each cilium and to assemble literally millions of these mechanisms into a ctenophore-like swimming device. It is possible, however, to distill and mimic key features of the actuator and control system ... 

Howard, Journal of Mechanics of Motor Proteins and the Cytoskeleton. Sinauer Ass. Inc., Sunderland, Massachusetts, 2001 (analysis of the molecular motors, cytoskeleton, and cells as a whole by using basic physical principles can be used for the development of undergraduate or graduate courses). 

Discuss the molecular motors operating close to equilibrium. 

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