98 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
Microbuckling of fibrin provides a mechanism for cell mechanosensing
Biological cells sense and respond to mechanical forces, but how such a mechanosensing process takes place in a nonlinear inhomogeneous fibrous matrix remains unknown. We show that cells in a fibrous matrix induce deformation fields that propagate over a longer range than predicted by linear elasticity. Synthetic, linear elastic hydrogels used in many mechanotransduction studies fail to capture this effect. We develop a nonlinear microstructural finite-element model for a fibre network to simulate localized deformations induced by cells. The model captures measured cell-induced matrix displacements from experiments and identifies an important mechanism for long-range cell mechanosensing: loss of compression stiffness owing to microbuckling of individual fibres. We show evidence that cells sense each other through the formation of localized intercellular bands of tensile deformations caused by this mechanism
Quantifying cell-induced matrix deformation in three dimensions based on imaging matrix fibers
During processes such as development and cancer metastasis, cells migrate into three-dimensional fibrous matrices. Previous studies have speculated on the mechanical forces required for migration by observing matrix fiber alignment, densification, and degradation, but these forces remain difficult to quantify. Here we present a new experimental technique to simultaneously measure full-field 3D displacements and structural remodeling of a fibrous matrix, both of which result from cellular forces. We apply this “2-in-1” experimental technique to follow single cells as they invade a physiologically relevant fibrin matrix. We find that cells generate tube-like structures in the matrix by plastically deforming their surroundings, and they re-use these tubes to extend protrusions. Cells generate these tubular structures by applying both pulling and pushing forces
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
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
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