Mechanism of unidirectional movement of kinesin motors

Kinesin motors have been studied extensively both experimentally and theoretically. However, the microscopic mechanism of the processive movement of kinesin is still an open question. In this paper, we propose a hand-over-hand model for the processivity of kinesin, which is based on chemical, mechanical, and electrical couplings. In the model the processive movement does not need to rely on the two heads' coordination in their ATP hydrolysis and mechanical cycles. Rather, the ATP hydrolyses at the two heads are independent. The much higher ATPase rate at the trailing head than the leading head makes the motor walk processively in a natural way, with one ATP being hydrolyzed per step. The model is consistent with the structural study of kinesin and the measured pathway of the kinesin ATPase. Using the model the estimated driving force of ~ 5.8 pN is in agreements with the experimental results (5~7.5 pN). The prediction of the moving time in one step (~10 microseconds) is also consistent with the measured values of 0~50 microseconds. The previous observation of substeps within the 8-nm step is explained. The shapes of velocity-load (both positive and negative) curves show resemblance to previous experimental results.Comment: 22 pages, 6 figure

Control of spiral waves and turbulent states in a cardiac model by travelling-wave perturbations

We propose a travelling-wave perturbation method to control the spatiotemporal dynamics in a cardiac model. It is numerically demonstrated that the method can successfully suppress the wave instability (alternans in action potential duration) in the one-dimensional case and convert spiral waves and turbulent states to the normal travelling wave states in the two-dimensional case. An experimental scheme is suggested which may provide a new design for a cardiac defibrillator.Comment: 9 pages, 5 figure

Model for processive movement of myosin V and myosin VI

Myosin V and myosin VI are two classes of two-headed molecular motors of the myosin superfamily that move processively along helical actin filaments in opposite directions. Here we present a hand-over-hand model for their processive movements. In the model, the moving direction of a dimeric molecular motor is automatically determined by the relative orientation between its two heads at free state and its head's binding orientation on track filament. This determines that myosin V moves toward the barbed end and myosin VI moves toward the pointed end of actin. During the moving period in one step, one head remains bound to actin for myosin V whereas two heads are detached for myosin VI: The moving manner is determined by the length of neck domain. This naturally explains the similar dynamic behaviors but opposite moving directions of myosin VI and mutant myosin V (the neck of which is truncated to only one-sixth of the native length). Because of different moving manners, myosin VI and mutant myosin V exhibit significantly broader step-size distribution than native myosin V. However, all three motors give the same mean step size of 36 nm (the pseudo-repeat of actin helix). Using the model we study the dynamics of myosin V quantitatively, with theoretical results in agreement with previous experimental ones.Comment: 18 pages, 7 figure

Induced Acceleration of Phosphine Exchange in Metal Carbonyls by Pendant Groups of Coordinated Polyphosphines

The kinetics and thermodynamics of isomerization of (OC)5CrPPh2CH2CH(PPh2)2 to its linkage isomer, (OC)5CrPPh2CH(PPh2)CH2PPh2, in chloroform-d have been studied with 31P{1H} NMR. (OC)5Cr[η1-PPh2CH2CH(PPh2)2] ⇄ (OC)5Cr[η1-PPh2CH(PPh2)CH2PPh2] The equilibrium constants for the reaction are 3.60, 2.61, 2.04, and 1.67 at 10 °C, 25 °C, 40 °C, and 53 °C, respectively. The forward reaction becomes more favorable as the temperature is decreased. The values of ΔH, ΔS, and ΔG(25 °C) were determined to be -13.6 kJ mol-1, -37.6 J mol-1K-1, and -2.4 kJ mol-1, respectively. The large decrease in entropy favors the reverse reaction while the decrease in enthalpy favors the forward reaction. Previous work has shown that for the analogous tungsten isomerization, values of ΔH, ΔS, and ΔG(25 °C) are -12.2 kJ mol-1, -28 J mol-1K-1, and -3.9 kJ mol-1, respectively.51 It can be concluded that the greater decrease in entropy for the chromium reaction accounts for its overall diminished favorableness as compared to the tungsten reaction. Rate constants for the forward reaction in chloroform at 10 °C, 25 °C, 40 °C are 2.0 x 10-7 s-1, 2.1 x 10-6 s-1, and 1.7 x 10-5 s-1 with half-lives to equilibrium of 31 days, 3 days, and 8 hours, respectively. These reactions are about an order of magnitude slower than the analogous tungsten reaction, but about four orders of magnitude faster than isomerization of (OC)5CrPPh2CH2CH2P(tol)2. 55c The enthalpy of activation, ΔH≠, for the forward and reverse reactions are 105 kJ mol-1 and 120 kJ mol-1, respectively, larger by 12 kJ mol-1 and 15 kJ mol-1 than observed for tungsten. The entropy of activation, ΔS≠, for the forward and reverse reactions were found to be 1.4 J mol-1K-1 and 40 J mol-1K-1, respectively. These values are considerably more positive than those obtained previously for tungsten (-28 J mol-1K-1 and -1.0 J mol-1K-1). It is concluded that abnormally fast isomerization rates for (OC)5MPPh2CH2CH(PPh2)2 (M = Cr, W) result because the short phosphine arm interacts with the equatorial carbonyl groups in the transition state, lowering the activation energy, and leading to labilization of the coordinated phosphorus atom which results in its replacement by the second phosphine arm. The concept of interaction between the short phosphine arm and the equatorial carbonyl groups is supported by long-range phosphorus-carbon coupling (4JPC), believed to augmented by a through-space mechanism. The entropies of activation suggest that phosphorus exchange in chromium has a much more significant dissociative component than for the analogous tungsten system. It would be expected that the smaller chromium atom would be less likely to form a stable 7-coordinate complex because of steric crowding. Complexes, (OC)5WPPh2C(PPh2)=CH2 and [(OC)5WPPh2]2C=CH2 have been synthesized for the first time. The crystal structure of the former compound has been determined. Unlike the similar (OC)5WPPh2CH2PPh2 complex, the dangling phosphorus atom is not directed toward the equatorial carbonyl groups and no long-range phosphorus-carbon coupling (4JPC) is observed

Dilemmatic Deliberations In Kierkegaard’s Fear and Trembling

My central claim in this paper is that Kierkegaard’s Fear and Trembling is governed by the basic aim to articulate a real dilemma, and to elicit its proper recognition as such. I begin by indicating how Kierkegaard’s works are shaped in general by this aim, and what the aim involves. I then show how the dilemmaticstructure of Fear and Trembling is obscured in a recent dispute between Michelle Kosch and John Lippitt regarding the basic aims and upshot of the book. Finally, I consider two critical questions: Why does Kierkegaard present his dilemmatic reasoning in the form of a “dialectical lyric”? And why does he write a book that aims only to articulate a dilemma, and not also to resolve it