158 research outputs found
Understanding Health and Disease with Multidimensional Single-Cell Methods
Current efforts in the biomedical sciences and related interdisciplinary
fields are focused on gaining a molecular understanding of health and disease,
which is a problem of daunting complexity that spans many orders of magnitude
in characteristic length scales, from small molecules that regulate cell
function to cell ensembles that form tissues and organs working together as an
organism. In order to uncover the molecular nature of the emergent properties
of a cell, it is essential to measure multiple cell components simultaneously
in the same cell. In turn, cell heterogeneity requires multiple cells to be
measured in order to understand health and disease in the organism. This review
summarizes current efforts towards a data-driven framework that leverages
single-cell technologies to build robust signatures of healthy and diseased
phenotypes. While some approaches focus on multicolor flow cytometry data and
other methods are designed to analyze high-content image-based screens, we
emphasize the so-called Supercell/SVM paradigm (recently developed by the
authors of this review and collaborators) as a unified framework that captures
mesoscopic-scale emergence to build reliable phenotypes. Beyond their specific
contributions to basic and translational biomedical research, these efforts
illustrate, from a larger perspective, the powerful synergy that might be
achieved from bringing together methods and ideas from statistical physics,
data mining, and mathematics to solve the most pressing problems currently
facing the life sciences.Comment: 25 pages, 7 figures; revised version with minor changes. To appear in
J. Phys.: Cond. Mat
A Microstructural View of Burrowing with RoboClam
RoboClam is a burrowing technology inspired by Ensis directus, the Atlantic
razor clam. Atlantic razor clams should only be strong enough to dig a few
centimeters into the soil, yet they burrow to over 70 cm. The animal uses a
clever trick to achieve this: by contracting its body, it agitates and locally
fluidizes the soil, reducing the drag and energetic cost of burrowing. RoboClam
technology, which is based on the digging mechanics of razor clams, may be
valuable for subsea applications that could benefit from efficient burrowing,
such as anchoring, mine detonation, and cable laying. We directly visualize the
movement of soil grains during the contraction of RoboClam, using a novel
index-matching technique along with particle tracking. We show that the size of
the failure zone around contracting RoboClam, can be theoretically predicted
from the substrate and pore fluid properties, provided that the timescale of
contraction is sufficiently large. We also show that the nonaffine motions of
the grains are a small fraction of the motion within the fluidized zone,
affirming the relevance of a continuum model for this system, even though the
grain size is comparable to the size of RoboClam
Effect of rare events on out of equilibrium relaxation
This letter reports experimental and numerical results on particle dynamics
in an out-of-equilibrium granular medium. We observed two distinct types of
grain motion: the well known cage motion, during which a grain is always
surrounded by the same neighbors, and low probability "jumps", during which a
grain moves significantly more relative to the others. These observations are
similar to the results obtained for other out-of-equilibrium systems (glasses,
colloidal systems, etc.). Although such jumps are extremely rare, by inhibiting
them in numerical simulations we demonstrate that they play a significant role
in the relaxation of out-of-equilibrium systemsComment: 4 pages, accepted for publication in Physical Review Letter
The path to fracture in granular flows: dynamics of contact networks
Capturing the dynamics of granular flows at intermediate length scales can
often be difficult. We propose studying the dynamics of contact networks as a
new tool to study fracture at intermediate scales. Using experimental
three-dimensional flow fields with particle-scale resolution, we calculate the
time evolving broken-links network and find that a giant component of this
network is formed as shear is applied to this system. We implement a model of
link breakages where the probability of a link breaking is proportional to the
average rate of longitudinal strain (elongation) in the direction of the edge
and find that the model demonstrates qualitative agreement with the data when
studying the onset of the giant component. We note, however, that the
broken-links network formed in the model is less clustered than our
experimental observations, indicating that the model reflects less localized
breakage events and does not fully capture the dynamics of the granular flow.Comment: 15 pages, 6 figures, accepted for publication in Phys. Rev.
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, 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
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