Clare C. Yu

The PCP Pathway Instructs the Planar Orientation of Ciliated Cells in the Xenopus Larval Skin

Planar cell polarity (PCP) is a property of epithelial tissues where cellular structures coordinately orient along a two-dimensional plane lying orthogonal to the axis of apical-basal polarity. PCP is particularly striking in tissues where multiciliate cells generate a directed fluid flow, as seen, for example, in the ciliated epithelia lining the respiratory airways or the ventricles of the brain. To produce directed flow, ciliated cells orient along a common planar axis in a direction set by tissue patterning, but how this is achieved in any ciliated epithelium is unknown. Here, we show that the planar orientation of Xenopus multiciliate cells is disrupted when components in the PCP-signaling pathway are altered non-cell-autonomously. We also show that wild-type ciliated cells located at a mutant clone border reorient toward cells with low Vangl2 or high Frizzled activity and away from those with high Vangl2 activity. These results indicate that the PCP pathway provides directional non-cell-autonomous cues to orient ciliated cells as they differentiate, thus playing a critical role in establishing directed ciliary flow.

Actin and microtubules drive differential aspects of planar cell polarity in multiciliated cells

Actin dynamics are required for proper cilia spacing, global coordination of cilia polarity, and coordination of metachronic cilia beating, whereas cytoplasmic microtubule dynamics are required for local coordination of polarity between neighboring cilia.

Mechanical stochastic tug-of-war models cannot explain bidirectional lipid-droplet transport

Intracellular transport via the microtubule motors kinesin and dynein plays an important role in maintaining cell structure and function. Often, multiple kinesin or dynein motors move the same cargo. Their collective function depends critically on the single motors’ detachment kinetics under load, which we experimentally measure here. This experimental constraint—combined with other experimentally determined parameters—is then incorporated into theoretical stochastic and mean-field models. Comparison of modeling results and in vitro data shows good agreement for the stochastic, but not mean-field, model. Many cargos in vivo move bidirectionally, frequently reversing course. Because both kinesin and dynein are present on the cargos, one popular hypothesis explaining the frequent reversals is that the opposite-polarity motors engage in unregulated stochastic tugs-of-war. Then, the cargos’ motion can be explained entirely by the outcome of these opposite-motor competitions. Here, we use fully calibrated stochastic and mean-field models to test the tug-of-war hypothesis. Neither model agrees well with our in vivo data, suggesting that, in addition to inevitable tugs-of-war between opposite motors, there is an additional level of regulation not included in the models.

How molecular motors are arranged on a cargo is important for vesicular transport.

The spatial organization of the cell depends upon intracellular trafficking of cargos hauled along microtubules and actin filaments by the molecular motor proteins kinesin, dynein, and myosin. Although much is known about how single motors function, there is significant evidence that cargos in vivo are carried by multiple motors. While some aspects of multiple motor function have received attention, how the cargo itself —and motor organization on the cargo—affects transport has not been considered. To address this, we have developed a three-dimensional Monte Carlo simulation of motors transporting a spherical cargo, subject to thermal fluctuations that produce both rotational and translational diffusion. We found that these fluctuations could exert a load on the motor(s), significantly decreasing the mean travel distance and velocity of large cargos, especially at large viscosities. In addition, the presence of the cargo could dramatically help the motor to bind productively to the microtubule: the relatively slow translational and rotational diffusion of moderately sized cargos gave the motors ample opportunity to bind to a microtubule before the motor/cargo ensemble diffuses out of range of that microtubule. For rapidly diffusing cargos, the probability of their binding to a microtubule was high if there were nearby microtubules that they could easily reach by translational diffusion. Our simulations found that one reason why motors may be approximately 100 nm long is to improve their ‘on’ rates when attached to comparably sized cargos. Finally, our results suggested that to efficiently regulate the number of active motors, motors should be clustered together rather than spread randomly over the surface of the cargo. While our simulation uses the specific parameters for kinesin, these effects result from generic properties of the motors, cargos, and filaments, so they should apply to other motors as well.

Decoherence of a Josephson qubit due to coupling to two-level systems

Noise and decoherence are major obstacles to the implementation of Josephson junction qubits in quantum computing. Recent experiments suggest that two-level systems (TLS) in the oxide tunnel barrier are a source of decoherence. We explore two decoherence mechanisms in which these two-level systems lead to the decay of Rabi oscillations that result when Josephson junction qubits are subjected to strong microwave driving. (A) We consider a Josephson qubit coupled resonantly to a two-level system, i.e., the qubit and TLS have equal energy splittings. As a result of this resonant interaction, the occupation probability of the excited state of the qubit exhibits beating. Decoherence of the qubit results when the two-level system decays from its excited state by emitting a phonon. (B) Fluctuations of the two-level systems in the oxide barrier produce fluctuations and

Microscopic Model of Critical Current Noise in Josephson Junctions

1∕f

Candidate Source of Flux Noise in SQUIDs: Adsorbed Oxygen Molecules.

noise in the Josephson junction critical current

Saturation of two-level systems and charge noise in Josephson junction qubits

{I}_{0}

Origin and Reduction of 1/f Magnetic Flux Noise in Superconducting Devices

. This in turn leads to fluctuations in the qubit energy splitting that degrade the qubit coherence. We compare our results with experiments on Josephson junction phase qubits.

Filament-Filament Switching Can Be Regulated by Separation Between Filaments Together with Cargo Motor Number

We present a simple microscopic model to show how fluctuating two-level systems in a Josephson junction tunnel barrier of thickness L can modify the potential energy of the barrier and produce critical current noise spectra. We find low frequency 1/f noise that goes as L5. Our values are in good agreement with recent experimental measurements of critical current noise in Al/AlOx/Al Josephson junctions. We also investigate the sensitivity of the noise on the nonuniformity of the tunnel barrier.