Quantifying stretching and rearrangement in epithelial sheet migration

Although understanding the collective migration of cells, such as that seen in epithelial sheets, is essential for understanding diseases such as metastatic cancer, this motion is not yet as well characterized as individual cell migration. Here we adapt quantitative metrics used to characterize the flow and deformation of soft matter to contrast different types of motion within a migrating sheet of cells. Using a Finite-Time Lyapunov Exponent (FTLE) analysis, we find that - in spite of large fluctuations - the flow field of an epithelial cell sheet is not chaotic. Stretching of a sheet of cells (i.e., positive FTLE) is localized at the leading edge of migration. By decomposing the motion of the cells into affine and non-affine components using the metric D$^{2}_{min}$, we quantify local plastic rearrangements and describe the motion of a group of cells in a novel way. We find an increase in plastic rearrangements with increasing cell densities, whereas inanimate systems tend to exhibit less non-affine rearrangements with increasing density.Comment: 21 pages, 7 figures This is an author-created, un-copyedited version of an article accepted for publication in the New Journal of Physics. IOP Publishing Ltd is not responsible for any errors or omissions in this version of the manuscript or any version derived from it. The Version of Record is available online at doi:10.1088/1367-2630/15/2/02503

Velocity statistics in excited granular media

We present an experimental study of velocity statistics for a partial layer of inelastic colliding beads driven by a vertically oscillating boundary. Over a wide range of parameters (accelerations 3-8 times the gravitational acceleration), the probability distribution P(v) deviates measurably from a Gaussian for the two horizontal velocity components. It can be described by P(v) ~ exp(-|v/v_c|^1.5), in agreement with a recent theory. The characteristic velocity v_c is proportional to the peak velocity of the boundary. The granular temperature, defined as the mean square particle velocity, varies with particle density and exhibits a maximum at intermediate densities. On the other hand, for free cooling in the absence of excitation, we find an exponential velocity distribution. Finally, we examine the sharing of energy between particles of different mass. The more massive particles are found to have greater kinetic energy.Comment: 27 pages, 13 figures, to appear in Chaos, September 99, revised 3 figures and tex

Diffusion of a granular pulse in a rotating drum

The diffusion of a pulse of small grains in an horizontal rotating drum is studied through discrete elements methods simulations. We present a theoretical analysis of the diffusion process in a one-dimensional confined space in order to elucidate the effect of the confining end-plate of the drum. We then show that the diffusion is neither subdiffusive nor superdiffusive but normal. This is demonstrated by rescaling the concentration profiles obtained at various stages and by studying the time evolution of the mean squared deviation. Finally we study the self-diffusion of both large and small grains and we show that it is normal and that the diffusion coefficient is independent of the grain size

Feedback control of unstable cellular solidification fronts

We present a numerical and experimental study of feedback control of unstable cellular patterns in directional solidification (DS). The sample, a dilute binary alloy, solidifies in a 2D geometry under a control scheme which applies local heating close to the cell tips which protrude ahead of the other. For the experiments, we use a real-time image processing algorithm to track cell tips, coupled with a movable laser spot array device, to heat locally. We show, numerically and experimentally, that spacings well below the threshold for a period-doubling instability can be stabilized. As predicted by the numerical calculations, cellular arrays become stable, and the spacing becomes uniform through feedback control which is maintained with minimal heating.Comment: 4 pages, 4 figures, 1 tabl

Particle dynamics in sheared granular matter

The particle dynamics and shear forces of granular matter in a Couette geometry are determined experimentally. The normalized tangential velocity $V(y)$ declines strongly with distance $y$ from the moving wall, independent of the shear rate and of the shear dynamics. Local RMS velocity fluctuations $\delta V(y)$ scale with the local velocity gradient to the power $0.4 \pm 0.05$. These results agree with a locally Newtonian, continuum model, where the granular medium is assumed to behave as a liquid with a local temperature $\delta V(y)^2$ and density dependent viscosity

Bubble kinematics in a sheared foam

We characterize the kinematics of bubbles in a sheared two-dimensional foam using statistical measures. We consider the distributions of both bubble velocities and displacements. The results are discussed in the context of the expected behavior for a thermal system and simulations of the bubble model. There is general agreement between the experiments and the simulation, but notable differences in the velocity distributions point to interesting elements of the sheared foam not captured by prevalent models

Universal and wide shear zones in granular bulk flow

We present experiments on slow granular flows in a modified (split-bottomed) Couette geometry in which wide and tunable shear zones are created away from the sidewalls. For increasing layer heights, the zones grow wider (apparently without bound) and evolve towards the inner cylinder according to a simple, particle-independent scaling law. After rescaling, the velocity profiles across the zones fall onto a universal master curve given by an error function. We study the shear zones also inside the material as function of both their local height and the total layer height.Comment: Minor corrections, accepted for PRL (4 pages, 6 figures

Creep motion in a granular pile exhibiting steady surface flow

We investigate experimentally granular piles exhibiting steady surface flow. Below the surface flow, it has been believed exisitence of a `frozen' bulk region, but our results show absence of such a frozen bulk. We report here that even the particles in deep layers in the bulk exhibit very slow flow and that such motion can be detected at an arbitrary depth. The mean velocity of the creep motion decays exponentially with depth, and the characteristic decay length is approximately equal to the particle-size and independent of the flow rate. It is expected that the creep motion we have seeen is observable in all sheared granular systems.Comment: 3 pages, 4 figure

From Cellular Characteristics to Disease Diagnosis: Uncovering Phenotypes with Supercells

Cell heterogeneity and the inherent complexity due to the interplay of multiple molecular processes within the cell pose difficult challenges for current single-cell biology. We introduce an approach that identifies a disease phenotype from multiparameter single-cell measurements, which is based on the concept of ‘‘supercell statistics’’, a single-cell-based averaging procedure followed by a machine learning classification scheme. We are able to assess the optimal tradeoff between the number of single cells averaged and the number of measurements needed to capture phenotypic differences between healthy and diseased patients, as well as between different diseases that are difficult to diagnose otherwise. We apply our approach to two kinds of single-cell datasets, addressing the diagnosis of a premature aging disorder using images of cell nuclei, as well as the phenotypes of two non-infectious uveitides (the ocular manifestations of Behc¸et’s disease and sarcoidosis) based on multicolor flow cytometry. In the former case, one nuclear shape measurement taken over a group of 30 cells is sufficient to classify samples as healthy or diseased, in agreement with usual laboratory practice. In the latter, our method is able to identify a minimal set of 5 markers that accurately predict Behc¸et’s disease and sarcoidosis. This is the first time that a quantitative phenotypic distinction between these two diseases has been achieved. To obtain this clear phenotypic signature, about one hundred CD8+ T cells need to be measured. Although the molecular markers identified have been reported to be important players in autoimmune disorders, this is the first report pointing out that CD8+ T cells can be used to distinguish two systemic inflammatory diseases. Beyond these specific cases, the approach proposed here is applicable to datasets generated by other kinds of state-of-the-art and forthcoming single-cell technologies, such as multidimensional mass cytometry, single-cell gene expression, and single-cell full genome sequencing techniques.Fil: Candia, Julian Marcelo. University of Maryland; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Física de Líquidos y Sistemas Biológicos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Física de Líquidos y Sistemas Biológicos; ArgentinaFil: Maunu, Ryan. University of Maryland; Estados UnidosFil: Driscoll, Meghan. University of Maryland; Estados UnidosFil: Biancotto, Angélique. National Institutes of Health; Estados UnidosFil: Dagur, Pradeep. National Institutes of Health; Estados UnidosFil: McCoy Jr., J Philip. National Institutes of Health; Estados UnidosFil: Nida Sen, H.. National Institutes of Health; Estados UnidosFil: Wei, Lai. National Institutes of Health; Estados UnidosFil: Maritan, Amos. Università di Padova; ItaliaFil: Cao, Kan. University of Maryland; Estados UnidosFil: Nussenblatt, Robert B. National Institutes of Health; Estados UnidosFil: Banavar, Jayanth R.. University of Maryland; Estados UnidosFil: Losert, Wolfgang. University of Maryland; Estados Unido