Quantum Impurities and the Neutron Resonance Peak in YBa2Cu3O7{\bf YBa_2 Cu_3 O_7}: Ni versus Zn

The influence of magnetic (S=1) and nonmagnetic (S=0) impurities on the spin dynamics of an optimally doped high temperature superconductor is compared in two samples with almost identical superconducting transition temperatures: YBa$_2$(Cu$_{0.97}$Ni$_{0.03}$)$_3$O$_7$ (T$_c$=80 K) and YBa$_2$(Cu$_{0.99}$Zn$_{0.01}$)$_3$O$_7$ (T$_c$=78 K). In the Ni-substituted system, the magnetic resonance peak (which is observed at E$_r \simeq$40 meV in the pure system) shifts to lower energy with a preserved E$_r$/T$_c$ ratio while the shift is much smaller upon Zn substitution. By contrast Zn, but not Ni, restores significant spin fluctuations around 40 meV in the normal state. These observations are discussed in the light of models proposed for the magnetic resonance peak.Comment: 3 figures, submitted to PR

Chemotaxis: a feedback-based computational model robustly predicts multiple aspects of real cell behaviour

The mechanism of eukaryotic chemotaxis remains unclear despite intensive study. The most frequently described mechanism acts through attractants causing actin polymerization, in turn leading to pseudopod formation and cell movement. We recently proposed an alternative mechanism, supported by several lines of data, in which pseudopods are made by a self-generated cycle. If chemoattractants are present, they modulate the cycle rather than directly causing actin polymerization. The aim of this work is to test the explanatory and predictive powers of such pseudopod-based models to predict the complex behaviour of cells in chemotaxis. We have now tested the effectiveness of this mechanism using a computational model of cell movement and chemotaxis based on pseudopod autocatalysis. The model reproduces a surprisingly wide range of existing data about cell movement and chemotaxis. It simulates cell polarization and persistence without stimuli and selection of accurate pseudopods when chemoattractant gradients are present. It predicts both bias of pseudopod position in low chemoattractant gradients and-unexpectedly-lateral pseudopod initiation in high gradients. To test the predictive ability of the model, we looked for untested and novel predictions. One prediction from the model is that the angle between successive pseudopods at the front of the cell will increase in proportion to the difference between the cell's direction and the direction of the gradient. We measured the angles between pseudopods in chemotaxing Dictyostelium cells under different conditions and found the results agreed with the model extremely well. Our model and data together suggest that in rapidly moving cells like Dictyostelium and neutrophils an intrinsic pseudopod cycle lies at the heart of cell motility. This implies that the mechanism behind chemotaxis relies on modification of intrinsic pseudopod behaviour, more than generation of new pseudopods or actin polymerization by chemoattractant

Actin Polymerization Controls the Organization of WASH Domains at the Surface of Endosomes

Sorting of cargoes in endosomes occurs through their selective enrichment into sorting platforms, where transport intermediates are generated. The WASH complex, which directly binds to lipids, activates the Arp2/3 complex and hence actin polymerization onto such sorting platforms. Here, we analyzed the role of actin polymerization in the physiology of endosomal domains containing WASH using quantitative image analysis. Actin depolymerization is known to enlarge endosomes. Using a novel colocalization method that is insensitive to the heterogeneity of size and shape of endosomes, we further show that preventing the generation of branched actin networks induces endosomal accumulation of the WASH complex. Moreover, we found that actin depolymerization induces a dramatic decrease in the recovery of endosomal WASH after photobleaching. This result suggests a built-in turnover, where the actin network, i.e. the product of the WASH complex, contributes to the dynamic exchange of the WASH complex by promoting its detachment from endosomes. Our experiments also provide evidence for a role of actin polymerization in the lateral compartmentalization of endosomes: several WASH domains exist at the surface of enlarged endosomes, however, the WASH domains coalesce upon actin depolymerization or Arp2/3 depletion. Branched actin networks are thus involved in the regulation of the size of WASH domains. The potential role of this regulation in membrane scission are discussed

Understanding eukaryotic chemotaxis: a pseudopod-centred view

Current descriptions of eukaryotic chemotaxis and cell movement focus on how extracellular signals (chemoattractants) cause new pseudopods to form. This 'signal-centred' approach is widely accepted but is derived mostly from special cases, particularly steep chemoattractant gradients. I propose a 'pseudopod-centred' explanation, whereby most pseudopods form themselves, without needing exogenous signals, and chemoattractants only bias internal pseudopod dynamics. This reinterpretation of recent data suggests that future research should focus on pseudopod mechanics, not signal processing

Propagating waves separate two states of actin organization in living cells

Propagating actin waves are dynamic supramolecular structures formed by the self-assembly of proteins within living cells. They are built from actin filaments together with single-headed myosin, the Arp2∕3 complex, and coronin in a defined three-dimensional order. The function of these waves in structuring the cell cortex is studied on the substrate-attached surface of Dictyostelium cells by the use of total internal reflection fluorescence (TIRF) microscopy. Actin waves separate two areas of the cell cortex from each other, which are distinguished by the arrangement of actin filaments. The Arp2∕3 complex dominates in the area enclosed by a wave, where it has the capacity of building dendritic structures, while the proteins prevailing in the external area, cortexillin I and myosin-II, bundle actin filaments and arrange them in antiparallel direction. Wave propagation is accompanied by transitions in the state of actin with a preferential period of 5 min. Wave generation is preceded by local fluctuations in actin assembly, some of the nuclei of polymerized actin emanating from clathrin-coated structures, others emerging independently. The dynamics of phase transitions has been analyzed to provide a basis for modeling the nonlinear interactions that produce spatio-temporal patterns in the actin system of living cells

Lamellipodia in Stationary and Fluctuating States

We review recent mathematical models describing the diffusive transport, reaction, and turnover of actin and regulators at the leading edge of motile cells. These models are motivated by experimental results using cells with flat, steady lamellipodia studied by Single Molecule Speckle microscopy. The same cells can also be made to exhibit protruding and retracting lamellipodia, which demonstrate how changes in actin polymerization lead to changes in the rate of protrusion. The second part of this chapter provides a description of these fluctuations as an excitable actin system pushing against the cell membrane by polymerization