93 research outputs found
Three-Dimensional Analysis of the Effect of Epidermal Growth Factor on Cell-Cell Adhesion in Epithelial Cell Clusters
The effect that growth factors such as epidermal growth factor (EGF) have on cell-cell adhesion is of interest in the study of cellular processes such as epithelial-mesenchymal transition. Because cell-cell adhesions cannot be measured directly, we use three-dimensional traction force microscopy to measure the tractions applied by clusters of MCF-10A cells to a compliant substrate beneath them before and after stimulating the cells with EGF. To better interpret the results, a finite element model, which simulates a cluster of individual cells adhered to one another and to the substrate with linear springs, is developed to better understand the mechanical interaction between the cells in the experiments. The experiments and simulations show that the cluster of cells acts collectively as a single unit, indicating that cell-cell adhesion remains strong before and after stimulation with EGF. In addition, the experiments and model emphasize the importance of three-dimensional measurements and analysis in these experiments
Cellular Contraction and Polarization Drive Collective Cellular Motion
Coordinated motions of close-packed multicellular systems typically generate cooperative packs, swirls, and clusters. These cooperative motions are driven by active cellular forces, but the physical nature of these forces and how they generate collective cellular motion remain poorly understood. Here, we study forces and motions in a confined epithelial monolayer and make two experimental observations: 1) the direction of local cellular motion deviates systematically from the direction of the local traction exerted by each cell upon its substrate; and 2) oscillating waves of cellular motion arise spontaneously. Based on these observations, we propose a theory that connects forces and motions using two internal state variables, one of which generates an effective cellular polarization, and the other, through contractile forces, an effective cellular inertia. In agreement with theoretical predictions, drugs that inhibit contractility reduce both the cellular effective elastic modulus and the frequency of oscillations. Together, theory and experiment provide evidence suggesting that collective cellular motion is driven by at least two internal variables that serve to sustain waves and to polarize local cellular traction in a direction that deviates systematically from local cellular velocity
On the integral cohomology of smooth toric varieties
Let be a smooth, not necessarily compact toric variety. We show
that a certain complex, defined in terms of the fan , computes the
integral cohomology of , including the module structure over the
homology of the torus. In some cases we can also give the product. As a
corollary we obtain that the cycle map from Chow groups to integral Borel-Moore
homology is split injective for smooth toric varieties. Another result is that
the differential algebra of singular cochains on the Borel construction of
is formal.Comment: 10 page
Stress-shape misalignment in confluent cell layers
This study investigates the relationship between cell shape and
cell-generated stresses in confluent cell layers. Using simultaneous
measurements of cell shape orientation and cell-generated contractile forces in
MDCK and LP-9 colonies, we report the emergence of correlated, dynamic domains
in which misalignment between the directors defined by cell shape and by
contractile forces reaches up to 90, effectively creating extensile domains
in a monolayer of contractile cells. To understand this misalignment, we
develop a continuum model that decouples the orientation of cell-generated
active forces from the orientation of the cell shapes. This challenges the
prevailing understanding that cells throughout a tissue create either
contractile or extensile forces, and the validity of the usual active nematic
models of cell motility where active forces are strictly slaved to cell shape
orientation.Comment: 10 pages, 6 figure
Graph products of spheres, associative graded algebras and Hilbert series
Given a finite, simple, vertex-weighted graph, we construct a graded
associative (non-commutative) algebra, whose generators correspond to vertices
and whose ideal of relations has generators that are graded commutators
corresponding to edges. We show that the Hilbert series of this algebra is the
inverse of the clique polynomial of the graph. Using this result it easy to
recognize if the ideal is inert, from which strong results on the algebra
follow. Non-commutative Grobner bases play an important role in our proof.
There is an interesting application to toric topology. This algebra arises
naturally from a partial product of spheres, which is a special case of a
generalized moment-angle complex. We apply our result to the loop-space
homology of this space.Comment: 19 pages, v3: elaborated on connections to related work, added more
citations, to appear in Mathematische Zeitschrif
Dense active matter model of motion patterns in confluent cell monolayers
Epithelial cell monolayers show remarkable displacement and velocity
correlations over distances of ten or more cell sizes that are reminiscent of
supercooled liquids and active nematics. We show that many observed features
can be described within the framework of dense active matter, and argue that
persistent uncoordinated cell motility coupled to the collective elastic modes
of the cell sheet is sufficient to produce swirl-like correlations. We obtain
this result using both continuum active linear elasticity and a normal modes
formalism, and validate analytical predictions with numerical simulations of
two agent-based cell models, soft elastic particles and the self-propelled
Voronoi model together with in-vitro experiments of confluent corneal
epithelial cell sheets. Simulations and normal mode analysis perfectly match
when tissue-level reorganisation occurs on times longer than the persistence
time of cell motility. Our analytical model quantitatively matches measured
velocity correlation functions over more than a decade with a single fitting
parameter.Comment: updated version accepted for publication in Nat. Com
Active wetting of epithelial tissues
Development, regeneration and cancer involve drastic transitions in tissue
morphology. In analogy with the behavior of inert fluids, some of these
transitions have been interpreted as wetting transitions. The validity and
scope of this analogy are unclear, however, because the active cellular forces
that drive tissue wetting have been neither measured nor theoretically
accounted for. Here we show that the transition between 2D epithelial
monolayers and 3D spheroidal aggregates can be understood as an active wetting
transition whose physics differs fundamentally from that of passive wetting
phenomena. By combining an active polar fluid model with measurements of
physical forces as a function of tissue size, contractility, cell-cell and
cell-substrate adhesion, and substrate stiffness, we show that the wetting
transition results from the competition between traction forces and contractile
intercellular stresses. This competition defines a new intrinsic lengthscale
that gives rise to a critical size for the wetting transition in tissues, a
striking feature that has no counterpart in classical wetting. Finally, we show
that active shape fluctuations are dynamically amplified during tissue
dewetting. Overall, we conclude that tissue spreading constitutes a prominent
example of active wetting --- a novel physical scenario that may explain
morphological transitions during tissue morphogenesis and tumor progression
The detailed 3D multi-loop aggregate/rosette chromatin architecture and functional dynamic organization of the human and mouse genomes
Unjamming and cell shape in the asthmatic airway epithelium
From coffee beans flowing in a chute to cells remodelling in a living tissue, a wide variety of close-packed collective systemsâ both inert and livingâhave the potential to jam. The collective can sometimes flow like a fluid or jam and rigidify like a solid. The unjammed-to-jammed transition remains poorly understood, however, and structural properties characterizing these phases remain unknown. Using primary human bronchial epithelial cells, we show that the jamming transition in asthma is linked to cell shape, thus establishing in that system a structural criterion for cell jamming. Surprisingly, the collapse of critical scaling predicts a counter-intuitive relationship between jamming, cell shape and cellâcell adhesive stresses that is borne out by direct experimental observations. Cell shape thus provides a rigorous structural signature for classification and investigation of bronchial epithelial layer jamming in asthma, and potentially in any process in disease or development in which epithelial dynamics play a prominent role
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