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Collective dynamics and force generation by cytoskeletal filaments are crucial in many cellular processes. Investigating growth dynamics of a bundle of N independent cytoskeletal filaments pushing against a wall, we show that chemical switching (ATP/GTP hydrolysis) leads to a collective phenomenon that is currently unknown. Obtaining force-velocity relations for different models that capture chemical switching, we show, analytically and numerically, that the collective stall force of N filaments is greater than N times the stall force of a single filament. Employing an exactly solvable toy model, we analytically prove the above result for N=2. We, further, numerically show the existence of this collective phenomenon, for N>=2, in realistic models (with random and sequential hydrolysis) that simulate actin and microtubule bundle growth. We make quantitative predictions for the excess forces, and argue that this collective effect is related to the non-equilibrium nature of chemical switching., New J. Phys., 2014

In this study, curcumin, a potential anticancer agent, was found to dampen the dynamic instability of individual microtubules in living MCF-7 cells. It strongly reduced the rate and extent of shortening states, and modestly reduced the rate and extent of growing states. In addition, curcumin decreased the fraction of time microtubules spent in the growing state and strongly increased the time microtubules spent in the pause state. Brief treatment with curcumin depolymerized mitotic microtubules, perturbed microtubule-kinetochore attachment and disturbed the mitotic spindle structure. Curcumin also perturbed the localization of the kinesin protein Eg5 and induced monopolar spindle formation. Further, curcumin increased the accumulation of Mad2 and BubR1 at the kinetochores, indicating that it activated the mitotic checkpoint. In addition, curcumin treatment increased the metaphase/anaphase ratio, indicating that it can delay mitotic progression from the metaphase to anaphase. We provide evidence suggesting that the affected cells underwent apoptosis via the p53-dependent apoptotic pathway. The results support the idea that kinetic stabilization of microtubule dynamics assists in the nuclear translocation of p53. Curcumin exerted additive effects when combined with vinblastine, a microtubule depolymerizing drug, whereas the combination of curcumin with paclitaxel, a microtubule-stabilizing drug, produced an antagonistic effect on the inhibition of MCF-7 cell proliferation. The results together suggested that curcumin inhibited MCF-7 cell proliferation by inhibiting the assembly dynamics of microtubules.

In this work, we investigate the stability of a continuous stirred tank reactor (CSTR) coupled to an isothermal, isobaric flash. The coupling is through the recycle of the reactant-rich stream from the downstream flash unit to the upstream reactor. We consider the first-order irreversible reaction A ? B occurring non-isothermally in the CSTR. The main focus of this work is to investigate the effect of delay arising as a result of transportation lag from the reactor to the separator on the system stability. In the absence of delay, it has been clearly shown that the coupled system exhibits static and dynamic instability. The effect of delay on the stability of the coupled system is studied for the two classical control strategies: (i) The fresh feed flow rate, F0, is flow controlled and the reactor effluent flow rate, F, is used to control the molar holdup in the reactor, MR. (ii) The flow rate, F, is flow controlled, and F0 is used to control MR. It is shown that delay induces new regions of dynamic instability. The system switches from instability to stability and vice versa for these two control strategies as the delay is increased. ? 2005 American Chemical Society.

In studies on the antiproliferative actions of coumarin compounds, we discovered that dicoumarol (a coumarin anticoagulant; 3,3'-methyl-enebis[4-hydroxycoumarin]) inhibits the first cleavage of Strongylocentrotus purpuratus (sea urchin) embryos in a concentration-dependent manner with 50% inhibition occurring at a concentration of 10 muM. Because first cleavage in sea urchin embryos is highly selective for microtubule-targeted agents, we thought that the active compounds might inhibit cell division by interacting with tubulin or microtubules. We found that dicoumarol binds to bovine brain tubulin with a K-d of 22 muM and that 0.1 muM dicoumarol strongly stabilizes the growing and shortening dynamics at the plus ends of the microtubules in vitro. Dicoumarol reduces the rate and extent of shortening, it increases the percentage of time the microtubules spend in an attenuated (paused) state, and it reduces the overall dynamicity of the microtubules. The antimitotic effects of the widely used cancer chemotherapeutic agent Taxol (paclitaxel) are also mediated by suppressing microtubule dynamics. We demonstrate that exposure to combinations of Taxol and dicoumarol results in a synergistic inhibition of cell division of sea urchin embryos. The results suggest that the antiproliferative mechanism of action of dicoumarol and possibly related pharmacophores may be mediated by tubulin binding and the stabilization of spindle microtubule dynamics. Because of its low toxicity and simple chemical structure, there is potential interest to explore combinations of antimitotic coumarins with other chemotherapeutic agents to improve efficacy and lower toxicity.

An investigation is carried out on the dynamic instability of anisotropic laminated composite plates considering geometric nonlinearity. The mathematical model is formulated using C� shear flexible, field consistent, QUAD-9 plate elements. The nonlinear governing equations are solved using the direct iteration technique. The effect of a large amplitude on the dynamic instability is studied for a simply-supported laminated composite plate. Detailed numerical results are presented for various parameters, namely, ply-angle, number of layers and thickness of plates. Copyright ? 1996 Elsevier Science Ltd.