Bidirectional cargo transport along microtubules is carried out by opposing teams of kinesin and dynein motors. Despite considerable study, the factors that determine whether these competing teams achieve net anterograde or retrograde transport in cells remain unclear. The goal of this work is to use stochastic simulations of bidirectional transport to determine the motor properties that most strongly determine overall cargo velocity and directionality. Simulations were carried out based on published optical tweezer characterization of kinesin-1 and kinesin-2, and for available data for cytoplasmic dynein and the dynein-dynactin-BicD2 (DDB) complex. By varying dynein parameters and analyzing cargo trajectories, we find that net cargo transport is predicted to depend minimally on the dynein stall force, but strongly on dynein load-dependent detachment kinetics. In simulations, dynein is dominated by kinesin-1, but DDB and kinesin-1 are evenly matched, recapitulating recent experimental work. Kinesin-2 competes less well against dynein and DDB, and overall, load-dependent motor detachment is the property that most determines a motor's ability to compete in bidirectional transport. It follows that the most effective intracellular regulators of bidirectional transport are predicted to be those that alter motor detachment kinetics rather than motor velocity or stall force. K E Y W O R D S axon, dynein, Kinesin, microtubule, motor protein, neuron, optical tweezer, single-molecule, transport, vesicle

Theoretical and experimental evidence for an effect of sieve tube turgor pressure on the mechanisms of phloem unloading near the root tips during moderate levels of drought stress is reviewed. An additional, simplified equation is proposed relating decreased turgor pressure to decreased rate kinetics of membrane bound transporters. The effect of such a mechanism would be to decrease phloem transport Speed, but increase Concentration and Pressure, and thus prevent or delay negative Pressure in the phloem. Experimental evidence shows this mechanism precedes and exceeds a reduction in stomatal conductance.

We propose a model of tumor-immune interaction with time delay in immune reaction and noise in tumor cell reproduction. Immune response is modeled as a non-monotonic function of tumor burden, for which the tumor is immunogenic at nascent stage but starts inhibiting immune system as it grows large. Without time delay and noise, this system demonstrates bistability. The effects of response time of the immune system and uncertainty in the tumor innate proliferation rate are studied by including delay and noise in the appropriate model terms. Stability, persistence and extinction of the tumor are analyzed. We find that delay and noise can both induce the transition from low tumor burden equilibrium to high tumor equilibrium. Moreover, our result suggests that the elimination of cancer depends on the basal level of the immune system rather than on its response speed to tumor growth.

Theoretical and experimental evidence for an effect of sieve tube turgor pressure on the mechanisms of phloem unloading near the root tips during moderate levels of drought stress is reviewed. An additional, simplified equation is proposed relating decreased turgor pressure to decreased rate kinetics of membrane bound transporters. The effect of such a mechanism would be to decrease phloem transport speed, but increase concentration and pressure, and thus prevent or delay negative pressure in the phloem. Experimental evidence shows this mechanism precedes and exceeds a reduction in stomatal conductance.

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