Auto-reverse nuclear migration in bipolar mammalian cells on micropatterned surfaces.

A novel assay based on micropatterning and time-lapse microscopy has been developed for the study of nuclear migration dynamics in cultured mammalian cells. When cultured on 10-20-microm wide adhesive stripes, the motility of C6 glioma and primary mouse fibroblast cells is diminished. Nevertheless, nuclei perform an unexpected auto-reverse motion: when a migrating nucleus approaches the leading edge, it decelerates, changes the direction of motion, and accelerates to move toward the other end of the elongated cell. During this process, cells show signs of polarization closely following the direction of nuclear movement. The observed nuclear movement requires a functioning microtubular system, as revealed by experiments disrupting the main cytoskeletal components with specific drugs. On the basis of our results, we argue that auto-reverse nuclear migration is due to forces determined by the interplay of microtubule dynamics and the changing position of the microtubule organizing center as the nucleus reaches the leading edge. Our assay recapitulates specific features of nuclear migration (cell polarization, oscillatory nuclear movement), while it allows the systematic study of a large number of individual cells. In particular, our experiments yielded the first direct evidence of reversive nuclear motion in mammalian cells, induced by attachment constraints.

Global organization of metabolic fluxes in the bacterium Escherichia coli.

Cellular metabolism, the integrated interconversion of thousands of metabolic substrates through enzyme-catalysed biochemical reactions, is the most investigated complex intracellular web of molecular interactions. Although the topological organization of individual reactions into metabolic networks is well understood, the principles that govern their global functional use under different growth conditions raise many unanswered questions. By implementing a flux balance analysis of the metabolism of Escherichia coli strain MG1655, here we show that network use is highly uneven. Whereas most metabolic reactions have low fluxes, the overall activity of the metabolism is dominated by several reactions with very high fluxes. E. coli responds to changes in growth conditions by reorganizing the rates of selected fluxes predominantly within this high-flux backbone. This behaviour probably represents a universal feature of metabolic activity in all cells, with potential implications for metabolic engineering.

Development of correlations in the dynamics of wet granular avalanches.

A detailed characterization of avalanche dynamics of wet granular media in a rotating drum apparatus is presented. The results confirm the existence of the three wetness regimes observed previously: the granular, the correlated, and the viscoplastic regime. These regimes show qualitatively different dynamic behaviors that are reflected in all the investigated quantities. We discuss the effect of interstitial liquid on the characteristic angles of the material and on the avalanche size distribution. These data also reveal logarithmic aging and allow us to map out the phase diagram of the dynamic behavior as a function of liquid content and flow rate. Via quantitative measurements of the flow velocity and the granular flux during avalanches, we characterize avalanche types unique to wet media. We also explore the details of viscoplastic flow (observed at the highest liquid contents) in which there are lasting contacts during flow, leading to coherence across the entire sample. This coherence leads to a velocity independent flow depth at high rotation rates and robust pattern formation in the granular surface.

Mexican waves in an excitable medium.

The Mexican wave, or La Ola, which rose to fame during the 1986 World Cup in Mexico, surges through the rows of spectators in a stadium as those in one section leap to their feet with their arms up, and then sit down again as the next section rises to repeat the motion. To interpret and quantify this collective human behaviour, we have used a variant of models that were originally developed to describe excitable media such as cardiac tissue. Modelling the reaction of the crowd to attempts to trigger the wave reveals how this phenomenon is stimulated, and may prove useful in controlling events that involve groups of excited people.

Avalanche dynamics in wet granular materials.

We have studied the dynamics of avalanching wet granular media in a rotating drum apparatus. Quantitative measurements of the flow velocity and the granular flux during avalanches allow us to characterize novel avalanche types unique to wet media. We also explore the details of viscoplastic flow (observed at the highest liquid contents) in which there are lasting contacts during flow, leading to coherence across the entire sample. This coherence leads to a velocity-independent flow depth at high rotation rates and novel robust pattern formation in the granular surface.

Stick-slip fluctuations in granular drag.

We study fluctuations in the drag force experienced by an object moving through a granular medium. The successive formation and collapse of jammed states give a stick-slip nature to the fluctuations which are periodic at small depths but become "stepped" at large depths, a transition that we interpret as a consequence of the long-range nature of the force chains and the finite size of our experiment. Another important finding is that the mean force and the fluctuations appear to be independent of the properties of the contact surface between the grains and the dragged object. These results imply that the drag force originates in the bulk properties of the granular sample.

Spectra of "real-world" graphs: beyond the semicircle law.

Many natural and social systems develop complex networks that are usually modeled as random graphs. The eigenvalue spectrum of these graphs provides information about their structural properties. While the semicircle law is known to describe the spectral densities of uncorrelated random graphs, much less is known about the spectra of real-world graphs, describing such complex systems as the Internet, metabolic pathways, networks of power stations, scientific collaborations, or movie actors, which are inherently correlated and usually very sparse. An important limitation in addressing the spectra of these systems is that the numerical determination of the spectra for systems with more than a few thousand nodes is prohibitively time and memory consuming. Making use of recent advances in algorithms for spectral characterization, here we develop methods to determine the eigenvalues of networks comparable in size to real systems, obtaining several surprising results on the spectra of adjacency matrices corresponding to models of real-world graphs. We find that when the number of links grows as the number of nodes, the spectral density of uncorrelated random matrices does not converge to the semicircle law. Furthermore, the spectra of real-world graphs have specific features, depending on the details of the corresponding models. In particular, scale-free graphs develop a trianglelike spectral density with a power-law tail, while small-world graphs have a complex spectral density consisting of several sharp peaks. These and further results indicate that the spectra of correlated graphs represent a practical tool for graph classification and can provide useful insight into the relevant structural properties of real networks.

Theory of periodic swarming of bacteria: application to Proteus mirabilis.

The periodic swarming of bacteria is one of the simplest examples for pattern formation produced by the self-organized collective behavior of a large number of organisms. In the spectacular colonies of Proteus mirabilis (the most common species exhibiting this type of growth), a series of concentric rings are developed as the bacteria multiply and swarm following a scenario that periodically repeats itself. We have developed a theoretical description for this process in order to obtain a deeper insight into some of the typical processes governing the phenomena in systems of many interacting living units. Our approach is based on simple assumptions directly related to the latest experimental observations on colony formation under various conditions. The corresponding one-dimensional model consists of two coupled differential equations investigated here both by numerical integrations and by analyzing the various expressions obtained from these equations using a few natural assumptions about the parameters of the model. We determine the phase diagram corresponding to systems exhibiting periodic swarming, and discuss in detail how the various stages of the colony development can be interpreted in our framework. We point out that all of our theoretical results are in excellent agreement with the complete set of available observations. Thus the present study represents one of the few examples where self-organized biological pattern formation is understood within a relatively simple theoretical approach, leading to results and predictions fully compatible with experiments.

Physics of the rhythmic applause.

We report on a series of measurements aimed to characterize the development and the dynamics of the rhythmic applause in concert halls. Our results demonstrate that while this process shares many characteristics of other systems that are known to synchronize, it also has features that are unexpected and unaccounted for in many other systems. In particular, we find that the mechanism lying at the heart of the synchronization process is the period doubling of the clapping rhythm. The characteristic interplay between synchronized and unsynchronized regimes during the applause is the result of a frustration in the system. All results are understandable in the framework of the Kuramoto model.

Simulating dynamical features of escape panic.

One of the most disastrous forms of collective human behaviour is the kind of crowd stampede induced by panic, often leading to fatalities as people are crushed or trampled. Sometimes this behaviour is triggered in life-threatening situations such as fires in crowded buildings; at other times, stampedes can arise during the rush for seats or seemingly without cause. Although engineers are finding ways to alleviate the scale of such disasters, their frequency seems to be increasing with the number and size of mass events. But systematic studies of panic behaviour and quantitative theories capable of predicting such crowd dynamics are rare. Here we use a model of pedestrian behaviour to investigate the mechanisms of (and preconditions for) panic and jamming by uncoordinated motion in crowds. Our simulations suggest practical ways to prevent dangerous crowd pressures. Moreover, we find an optimal strategy for escape from a smoke-filled room, involving a mixture of individualistic behaviour and collective 'herding' instinct.

Freezing by heating in a driven mesoscopic system

We investigate a simple model corresponding to particles driven in opposite directions and interacting via a repulsive potential. The particles move off-lattice on a periodic strip and are subject to random forces as well. We show that this model-which can be considered as a continuum version of some driven diffusive systems-exhibits a paradoxical, new kind of transition called here "freezing by heating." One interesting feature of this transition is that a crystallized state with a higher total energy is obtained from a fluid state by increasing the amount of fluctuations.

Jamming and fluctuations in granular drag

We investigate the dynamic evolution of jamming in granular media through fluctuations in the granular drag force. The successive collapse and formation of jammed states give a stick-slip nature to the fluctuations which is independent of the contact surface between the grains and the dragged object, thus implying that the stress-induced collapse is nucleated in the bulk of the granular sample. We also find that while the fluctuations are periodic at small depths, they become "stepped" at large depths, a transition which we interpret as a consequence of the long-range nature of the force chains.

Proliferative and migratory responses of astrocytes to in vitro injury.

An in vitro "scratch-wound" model was used to evoke and investigate some astroglial responses to mechanical injury. The changes in the morphology, locomotion, and proliferation of injured astrocytes were analysed under culture conditions devoid of blood-derived cells responsible for activating the inflammatory cascade. The rate of proliferation was determined by immunocytochemical detection of BrdU-incorporating cells located next to or far from the wound. The motility of individual cells and the mass-advancement of cell-assemblies were monitored by computer controlled video-microscopy both in injured monolayers and in preparations of single cells or aggregates of astrocytes. The large sets of digitalized data allowed a reliable statistical evaluation of changes in cell positions providing a quantitative approach for studies on dynamics of cell locomotion. The results indicated that cultivated astrocytes respond to injury (1) with enhanced nestin immunoreactivity at the expanding processes, (2) with increased mitotic activity exceeding the rate caused by the liberation from contact inhibition, but (3) without specific, injury-induced activation of cell locomotion. Some advantages and drawbacks of "scratch-wound" models of astrocytic responses to mechanical injury are presented and discussed.

Dynamics of cell aggregation during in vitro neurogenesis by immortalized neuroectodermal progenitors.

Early events of in vitro neuronal development were studied by inducing neuron formation in a neuroectodermal cell line, NE-4C/A3, derived from the embryonic forebrain vesicles of p53-deficient mice. Neuronal differentiation was initiated by treating the cells with all-trans retinoic acid (RA). By the second day of RA treatment compact cell aggregates were formed. The first signs of neuronal cell fate decision were revealed inside the aggregates. To elucidate the process of aggregate formation, the dynamics of cell clustering and the migration of individual cells were investigated by a novel computer-controlled videomicroscopic system. Besides real-time observation of cell motility, the system allowed statistical analysis of large sets of data providing quantitative evaluation of cell locomotion during an early, critical phase of RA induced neuron formation. The results showed that chemoattractants did not play a principal role in cell aggregation. Retinoic acid, on the other hand, was found to cause a rapid decrease in the average migratory velocity without changing the randomness of migratory routes. The data indicated that aggregation was facilitated by increased cohesion upon incident collision of randomly encountering cells. The resulting compact cell clusters provided the structural conditions for contact communication apparently needed for the neuronal differentiation of NE-4C/A3 cells.

Locomotion and proliferation of glioblastoma cells in vitro: statistical evaluation of videomicroscopic observations.

OBJECT: The motility and doubling of human glioblastoma cells were investigated by means of statistical evaluation of large sets of data obtained using computer-aided videomicroscopy. METHODS: Data were obtained on cells in four established glioblastoma cell lines and also on primary tumor cells cultured from fresh surgical samples. Growth rates and cell cycle times were measured in individual microscopic fields. The averages of cell cycle time and the duplication time for the recorded cell populations were 26.2 +/- 5.6 hours and 38 +/- 4 hours, respectively. With these parameters, no significant differences among the cell lines were revealed. Also, there was no correlation in the cell cycle time of a parent cell and its progeny in any of the cultures. Statistical analysis of cell locomotion revealed an exponential distribution of cell velocities and strong fluctuations in individual cell velocities across time. The average velocity values ranged from 4.2 to 27.9 micro/hour. In spite of the uniform histopathological classification of the four tumors, each cell line produced by these tumors displayed distinct velocity distribution profiles and characteristic average velocity values. A comparison of recently established primary cultures with cell lines that had propagated multiple times indicated that cells derived from different tumors sustain their characteristic locomotor activity after several passages. CONCLUSIONS: It can be inferred from the data that statistical evaluation of physical parameters of cell locomotion can provide additional tools for tumor diagnosis.

Liquid-induced transitions in granular media.

We investigate the effect of interstitial liquid on the physical properties of granular media by measuring the angle of repose as a function of the liquid content. The resultant adhesive forces lead to three distinct regimes in the observed behavior as the liquid content is increased: a granular regime in which the grains move individually, a correlated regime in which the grains move in correlated clusters, and a plastic regime in which the grains flow coherently. We discuss these regimes in terms of two proposed theories describing the effects of liquid on the physical properties of granular media.

Transitions in the horizontal transport of vertically vibrated granular layers.

Motivated by recent advances in the investigation of fluctuation-driven ratchets and flows in excited granular media, we have carried out experimental and simulational studies to explore the horizontal transport of granular particles in a vertically vibrated system whose base has a sawtooth-shaped profile. The resulting material flow exhibits novel collective behavior, both as a function of the number of layers of particles and the driving frequency; in particular, under certain conditions, increasing the layer thickness leads to a reversal of the current, while the onset of transport as a function of frequency occurs gradually in a manner reminiscent of a phase transition. Our experimental findings are interpreted here with the help of extensive, event driven Molecular Dynamics simulations. In addition to reproducing the experimental results, the simulations revealed that the current may be reversed as a function of the driving frequency as well. We also give details about the simulations so that similar numerical studies can be carried out in a more straightforward manner in the future.