73 research outputs found
Role of turn-over in active stress generation in a filament network
We study the effect of turnover of cross linkers, motors and filaments on the
generation of a contractile stress in a network of filaments connected by
passive crosslinkers and subjected to the forces exerted by molecular motors.
We perform numerical simulations where filaments are treated as rigid rods and
molecular motors move fast compared to the timescale of exchange of
crosslinkers. We show that molecular motors create a contractile stress above a
critical number of crosslinkers. When passive crosslinkers are allowed to turn
over, the stress exerted by the network vanishes, due to the formation of
clusters. When both filaments and passive crosslinkers turn over, clustering is
prevented and the network reaches a dynamic contractile steady-state. A maximum
stress is reached for an optimum ratio of the filament and crosslinker turnover
rates.Comment: 17 pages, 8 figures, 5 supplementary movies (included in the source)
In the latest version, appendices D and E have been added, text has been
updated, Figure 2 has been corrected, and Figure 4 has been replaced by
simulation results with higher precisio
Stability and roughness of interfaces in mechanically-regulated tissues
Cell division and death can be regulated by the mechanical forces within a
tissue. We study the consequences for the stability and roughness of a
propagating interface, by analysing a model of mechanically-regulated tissue
growth in the regime of small driving forces. For an interface driven by
homeostatic pressure imbalance or leader-cell motility, long and
intermediate-wavelength instabilities arise, depending respectively on an
effective viscosity of cell number change, and on substrate friction. A further
mechanism depends on the strength of directed motility forces acting in the
bulk. We analyse the fluctuations of a stable interface subjected to cell-level
stochasticity, and find that mechanical feedback can help preserve
reproducibility at the tissue scale. Our results elucidate mechanisms that
could be important for orderly interface motion in developing tissues.Comment: Final author version, In press at Phys. Rev. Lett., supplement is
available at:
https://www.dropbox.com/s/p5mwzdxlw40eglv/supplement_28Nov.pdf?dl=0 or
contact author
A Three-Dimensional Numerical Model of an Active Cell Cortex in the Viscous Limit
The cell cortex is a highly dynamic network of cytoskeletal filaments in which motor proteins induce active cortical stresses which in turn drive dynamic cellular processes such as cell motility, furrow formation or cytokinesis during cell division. Here, we develop a three-dimensional computational model of a cell cortex in the viscous limit including active cortical flows. Combining active gel and thin shell theory, we base our computational tool directly on the force balance equations for the velocity field on a discretized and arbitrarily deforming cortex. Since our method is based on the general force balance equations, it can easily be extended to more complex biological dependencies in terms of the constitutive laws or a dynamic coupling to a suspending fluid. We validate our algorithm by investigating the formation of a cleavage furrow on a biological cell immersed in a passive outer fluid, where we successfully compare our results to axi-symmetric simulations. We then apply our fully three-dimensional algorithm to fold formation and to study furrow formation under the influence of non-axisymmetric disturbances such as external shear. We report a reorientation mechanism by which the cell autonomously realigns its axis perpendicular to the furrow plane thus contributing to the robustness of cell division under realistic environmental conditions
First passage time distribution of active thermal particles in potentials
We introduce a perturbative method to calculate all moments of the
first-passage time distribution in stochastic one-dimensional processes which
are subject to both white and coloured noise. This class of non-Markovian
processes is at the centre of the study of thermal active matter, that is
self-propelled particles subject to diffusion. The perturbation theory about
the Markov process considers the effect of self-propulsion to be small compared
to that of thermal fluctuations. To illustrate our method, we apply it to the
case of active thermal particles (i) in a harmonic trap (ii) on a ring. For
both we calculate the first-order correction of the moment-generating function
of first-passage times, and thus to all its moments. Our analytical results are
compared to numerics.Comment: 25 pages, 10 figure
Field theory of survival probabilities, extreme values, first passage times, and mean span of non-Markovian stochastic processes
We provide a perturbative framework to calculate extreme events of
non-Markovian processes, by mapping the stochastic process to a two-species
reaction diffusion process in a Doi-Peliti field theory combined with the
Martin-Siggia-Rose formalism. This field theory treats interactions and the
effect of external, possibly self-correlated noise in a perturbation about a
Markovian process, thereby providing a systematic, diagrammatic approach to
extreme events. We apply the formalism to Brownian Motion and calculate its
survival probability distribution subject to self-correlated noise.Comment: 24 pages, 4 figures; added figures, comments and reference
Triangles bridge the scales: Quantifying cellular contributions to tissue deformation
In this article, we propose a general framework to study the dynamics and
topology of cellular networks that capture the geometry of cell packings in
two-dimensional tissues. Such epithelia undergo large-scale deformation during
morphogenesis of a multicellular organism. Large-scale deformations emerge from
many individual cellular events such as cell shape changes, cell
rearrangements, cell divisions, and cell extrusions. Using a triangle-based
representation of cellular network geometry, we obtain an exact decomposition
of large-scale material deformation. Interestingly, our approach reveals
contributions of correlations between cellular rotations and elongation as well
as cellular growth and elongation to tissue deformation. Using this Triangle
Method, we discuss tissue remodeling in the developing pupal wing of the fly
Drosophila melanogaster.Comment: 26 pages, 18 figure
Active dynamics of tissue shear flow
We present a hydrodynamic theory to describe shear flows in developing
epithelial tissues. We introduce hydrodynamic fields corresponding to state
properties of constituent cells as well as a contribution to overall tissue
shear flow due to rearrangements in cell network topology. We then construct a
generic linear constitutive equation for the shear rate due to topological
rearrangements and we investigate a novel rheological behaviour resulting from
memory effects in the tissue. We identify two distinct active cellular
processes: generation of active stress in the tissue, and actively driven
topological rearrangements. We find that these two active processes can produce
distinct cellular and tissue shape changes, depending on boundary conditions
applied on the tissue. Our findings have consequences for the understanding of
tissue morphogenesis during development
Myosin II Controls Junction Fluctuations to Guide Epithelial Tissue Ordering.
Under conditions of homeostasis, dynamic changes in the length of individual adherens junctions (AJs) provide epithelia with the fluidity required to maintain tissue integrity in the face of intrinsic and extrinsic forces. While the contribution of AJ remodeling to developmental morphogenesis has been intensively studied, less is known about AJ dynamics in other circumstances. Here, we study AJ dynamics in an epithelium that undergoes a gradual increase in packing order, without concomitant large-scale changes in tissue size or shape. We find that neighbor exchange events are driven by stochastic fluctuations in junction length, regulated in part by junctional actomyosin. In this context, the developmental increase of isotropic junctional actomyosin reduces the rate of neighbor exchange, contributing to tissue order. We propose a model in which the local variance in tension between junctions determines whether actomyosin-based forces will inhibit or drive the topological transitions that either refine or deform a tissue
Steering cell migration by alternating blebs and actin-rich protrusions.
BACKGROUND: High directional persistence is often assumed to enhance the efficiency of chemotactic migration. Yet, cells in vivo usually display meandering trajectories with relatively low directional persistence, and the control and function of directional persistence during cell migration in three-dimensional environments are poorly understood. RESULTS: Here, we use mesendoderm progenitors migrating during zebrafish gastrulation as a model system to investigate the control of directional persistence during migration in vivo. We show that progenitor cells alternate persistent run phases with tumble phases that result in cell reorientation. Runs are characterized by the formation of directed actin-rich protrusions and tumbles by enhanced blebbing. Increasing the proportion of actin-rich protrusions or blebs leads to longer or shorter run phases, respectively. Importantly, both reducing and increasing run phases result in larger spatial dispersion of the cells, indicative of reduced migration precision. A physical model quantitatively recapitulating the migratory behavior of mesendoderm progenitors indicates that the ratio of tumbling to run times, and thus the specific degree of directional persistence of migration, are critical for optimizing migration precision. CONCLUSIONS: Together, our experiments and model provide mechanistic insight into the control of migration directionality for cells moving in three-dimensional environments that combine different protrusion types, whereby the proportion of blebs to actin-rich protrusions determines the directional persistence and precision of movement by regulating the ratio of tumbling to run times.This work was supported by the Max Planck Society, the Medical Research
Council UK (core funding to the MRC LMCB), and by grants from the Polish
Ministry of Science and Higher Education (454/N-MPG/2009/0) to EKP, the
Deutsche Forschungsgemeinschaft (HE 3231/6-1 and PA 1590/1-1) to CPH
and EKP, a A*Star JCO career development award (12302FG010) to WY and a
Damon Runyon fellowship award to ADM (DRG 2157-12). This work was also
supported by the Francis Crick Institute which receives its core funding from
Cancer Research UK (FC001317), the UK Medical Research Council
(FC001317), and the Wellcome Trust (FC001317) to G
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