3,066 research outputs found
Dynamics of membranes driven by actin polymerization
A motile cell, when stimulated, shows a dramatic increase in the activity of
its membrane, manifested by the appearance of dynamic membrane structures such
as lamellipodia, filopodia and membrane ruffles. The external stimulus turns on
membrane bound activators, like Cdc42 and PIP2, which cause increased branching
and polymerization of the actin cytoskeleton in their vicinity leading to a
local protrusive force on the membrane. The emergence of the complex membrane
structures is a result of the coupling between the dynamics of the membrane,
the activators and the protrusive forces. We present a simple model that treats
the dynamics of a membrane under the action of actin polymerization forces that
depend on the local density of freely diffusing activators on the membrane. We
show that, depending on the spontaneous membrane curvature associated with the
activators, the resulting membrane motion can be wave-like, corresponding to
membrane ruffling and actin-waves, or unstable, indicating the tendency of
filopodia to form. Our model also quantitatively explains a variety of related
experimental observations and makes several testable predictions.Comment: 37 pages, 8 figures, revte
The patterning and functioning of protrusive activity during convergence and extension of the Xenopus organiser
We discuss the cellular basis and tissue interactions regulating
convergence and extension of the vertebrate
body axis in early embryogenesls of Xenopus. Convergence
and extension occur in the dorsal mesoderm
(prospective notochord and somite) and in the posterior
nervous system (prospective hindbrain and spinal cord)
by sequential cell intercalations. Several layers of cells
intercalate to form a thinner, longer array (radial intercalation)
and then cells intercalate in the mediolateral
orientation to form a longer, narrower array (mediolateral
intercalation). Fluorescence microscopy of
labeled mesodermal cells in explants shows that protrusive
activity is rapid and randomly directed until the
midgastrula stage, when it slows and is restricted to the
medial and lateral ends of the cells. This bipolar protrusive
activity results in elongation, alignment and
mediolateral intercalation of the cells. Mediolateral
intercalation behavior (MIB) is expressed in an anterior-
posterior and lateral-medial progression in the
mesoderm. MIB is first expressed laterally in both
somitic and notochordal mesoderm. From its lateral origins
in each tissue, MIB progresses medially. If convergence
does not bring the lateral boundaries of the tissues
closer to the medial cells in the notochordal and somitic
territories, these cells do not express MIB. Expression
of tissue-specific markers follows and parallels the
expression of MIB. These facts argue that MIB and
some aspects of tissue differentiation are induced by signals
emanating from the lateral boundaries of the tissue
territories and that convergence must bring medial cells
and boundaries closer together for these signals to be
effective. Grafts of dorsal marginal zone epithelium to
the ventral sides of other embryos, to ventral explants
and to UV-ventralized embryos show that it has a role
in organising convergence and extension, and dorsal
tissue differentiation among deep mesodermal cells.
Grafts of involuting marginal zone to animal cap tissue
of the early gastrula shows that convergence and extension
of the hindbrain-spinal cord are induced by planar
signals from the involuting marginal zone
Border forces and friction control epithelial closure dynamics
Epithelization, the process whereby an epithelium covers a cell-free surface,
is not only central to wound healing but also pivotal in embryonic
morphogenesis, regeneration, and cancer. In the context of wound healing, the
epithelization mechanisms differ depending on the sizes and geometries of the
wounds as well as on the cell type while a unified theoretical decription is
still lacking. Here, we used a barrier-based protocol that allows for making
large arrays of well-controlled circular model wounds within an epithelium at
confluence, without injuring any cells. We propose a physical model that takes
into account border forces, friction with the substrate, and tissue rheology.
Despite the presence of a contractile actomyosin cable at the periphery of the
wound, epithelization was mostly driven by border protrusive activity. Closure
dynamics was quantified by an epithelization coefficient
defined as the ratio of the border protrusive stress to the friction
coefficient between epithelium and substrate. The same assay and model
showed a high sensitivity to the RasV12 mutation on human epithelial cells,
demonstrating the general applicability of the approach and its potential to
quantitatively characterize metastatic transformations.Comment: 44 pages, 17 figure
A stochastic model for protrusion activity
In this work we approach cell migration under a large-scale assumption, so
that the system reduces to a particle in motion. Unlike classical particle
models, the cell displacement results from its internal activity: the cell
velocity is a function of the (discrete) protrusive forces exerted by filopodia
on the substrate. Cell polarisation ability is modeled in the feedback that the
cell motion exerts on the protrusion rates: faster cells form preferentially
protrusions in the direction of motion. By using the mathematical framework of
structured population processes previously developed to study population
dynamics [Fournier and M{\'e}l{\'e}ard, 2004], we introduce rigorously the
mathematical model and we derive some of its fundamental properties. We perform
numerical simulations on this model showing that different types of
trajectories may be obtained: Brownian-like, persistent, or intermittent when
the cell switches between both previous regimes. We find back the trajectories
usually described in the literature for cell migration
Modelling cell motility and chemotaxis with evolving surface finite elements
We present a mathematical and a computational framework for the modelling of cell motility. The cell membrane is represented by an evolving surface, with the movement of the cell determined by the interaction of various forces that act normal to the surface. We consider external forces such as those that may arise owing to inhomogeneities in the medium and a pressure that constrains the enclosed volume, as well as internal forces that arise from the reaction of the cells' surface to stretching and bending. We also consider a protrusive force associated with a reaction-diffusion system (RDS) posed on the cell membrane, with cell polarization modelled by this surface RDS. The computational method is based on an evolving surface finite-element method. The general method can account for the large deformations that arise in cell motility and allows the simulation of cell migration in three dimensions. We illustrate applications of the proposed modelling framework and numerical method by reporting on numerical simulations of a model for eukaryotic chemotaxis and a model for the persistent movement of keratocytes in two and three space dimensions. Movies of the simulated cells can be obtained from http://homepages.warwick.ac.uk/maskae/CV_Warwick/Chemotaxis.html
Cell motility driving mediolateral intercalation in explants of Xenopus laevis
In Xenopus, convergence and extension are produced by active intercalation of the deep mesodermal cells between one another along the mediolateral axis (mediolateral cell intercalation), to form a narrower, longer array. The cell motility driving this intercalation is poorly understood. A companion paper shows that the endodermal epithelium organizes the outermost mesodermal cells immediately beneath it to undergo convergence and extension, and other evidence suggests that these deep cells are the most active participants in mediolateral intercalation (Shih, J. and Keller, R. (1992) Development 116, 887–899). In this paper, we shave off the deeper layers of mesodermal cells, which allows us to observe the protrusive activity of the mesodermal cells next to the organizing epithelium with high resolution video microscopy. These mesodermal cells divide in the early gastrula and show rapid, randomly directed protrusive activity. At the early midgastrula stage, they begin to express a characteristic sequence of behaviors, called mediolateral intercalation behavior (MIB): (1) large, stable, filiform and lamelliform protrusions form in the lateral and medial directions, thus making the cells bipolar; (2) these protrusions are applied directly to adjacent cell surfaces and exert traction on them, without contact inhibition; (3) as a result, the cells elongate and align parallel to the mediolateral axis and perpendicular to the axis of extension; (4) the elongate, aligned cells intercalate between one another along the mediolateral axis, thus producing a longer, narrower array. Explants of essentially a single layer of deep mesodermal cells, made at stage 10.5, converge and extend by mediolateral intercalation. Thus by stage 10.5 (early midgastrula), expression of MIB among deep mesodermal cells is physiologically and mechanically independent of the organizing influence of the endodermal epithelium, described previously (Shih, J. and Keller, R. (1992) Development 116 887–899), and is the fundamental cell motility underlying mediolateral intercalation and convergence and extension of the body axis
The distribution of Dishevelled in convergently extending mesoderm
Convergent extension (CE) is a conserved morphogenetic movement that drives axial lengthening of the primary body axis and depends on the planar cell polarity (PCP) pathway. In Drosophila epithelia, a polarised subcellular accumulation of PCP core components, such as Dishevelled (Dvl) protein, is associated with PCP function. Dvl has long been thought to accumulate in the mediolateral protrusions in Xenopus chordamesoderm cells undergoing CE. Here we present a quantitative analysis of Dvl intracellular localisation in Xenopus chordamesoderm cells. We find that, surprisingly, accumulations previously observed at mediolateral protrusions of chordamesodermal cells are not protrusion-specific but reflect yolk-free cytoplasm and are quantitatively matched by the distribution of the cytoplasm-filling lineage marker dextran. However, separating cell cortex-associated from bulk Dvl signal reveals a statistical enrichment of Dvl in notochord–somite boundary-(NSB)-directed protrusions, which is dependent upon NSB proximity. Dvl puncta were also observed, but only upon elevated overexpression. These puncta showed no statistically significant spatial bias, in contrast to the strongly posteriorly-enriched GFP-Dvl puncta previously reported in zebrafish. We propose that Dvl distribution is more subtle and dynamic than previously appreciated and that in vertebrate mesoderm it reflects processes other than protrusion as such
- …