34 research outputs found
Interplay between substrate rigidity and tissue fluidity regulates cell monolayer spreading
Coordinated and cooperative motion of cells is essential for embryonic
development, tissue morphogenesis, wound healing and cancer invasion. A
predictive understanding of the emergent mechanical behaviors in collective
cell motion is challenging due to the complex interplay between cell-cell
interactions, cell-matrix adhesions and active cell behaviors. To overcome this
challenge, we develop a predictive cellular vertex model that can delineate the
relative roles of substrate rigidity, tissue mechanics and active cell
properties on the movement of cell collectives. We apply the model to the
specific case of collective motion in cell aggregates as they spread into a
two-dimensional cell monolayer adherent to a soft elastic matrix. Consistent
with recent experiments, we find that substrate stiffness regulates the driving
forces for the spreading of cellular monolayer, which can be pressure-driven or
crawling-based depending on substrate rigidity. On soft substrates, cell
monolayer spreading is driven by an active pressure due to the influx of cells
coming from the aggregate, whereas on stiff substrates, cell spreading is
driven primarily by active crawling forces. Our model predicts that cooperation
of cell crawling and tissue pressure drives faster spreading, while the
spreading rate is sensitive to the mechanical properties of the tissue. We find
that solid tissues spread faster on stiff substrates, with spreading rate
increasing with tissue tension. By contrast, the spreading of fluid tissues is
independent of substrate stiffness and is slower than solid tissues. We compare
our theoretical results with experimental results on traction force generation
and spreading kinetics of cell monolayers, and provide new predictions on the
role of tissue fluidity and substrate rigidity on collective cell motion.Comment: revised paper title, more references adde
Finite Elasticity of the Vertex Model and its Role in Rigidity of Curved Cellular Tissues
Using a mean field approach and simulation, we study the non-linear
mechanical response of the vertex model (VM) of biological tissue under
compression and dilation. The VM is known to exhibit a transition between rigid
and fluid-like, or floppy, states driven by geometric incompatibility. Target
perimeter and area set a target shape which may not be geometrically
achievable, thereby engendering frustration. Previously, an asymmetry in the
linear elastic response was identified at the rigidity transition between
compression and dilation. Here we show and characterize how the asymmetry
extends away from the transition point for finite strains. Under finite
compression, an initially solid VM can totally relax perimeter tension, and
thereby have reduced bulk and shear modulus. Conversely, an initially floppy VM
under dilation can rigidify and have a higher bulk and shear modulus. These
observations imply that re-scaling of cell area shifts the transition between
rigid and floppy states. Based on this insight, we calculate the re-scaling of
cell area engendered by intrinsic curvature and write a prediction for the
rigidity transition in the presence of curvature. The shift of the rigidity
transition in the presence of curvature for the VM provides a new metric for
predicting tissue rigidity from image data for curved tissues in a manner
analogous to the flat case.Comment: 10 pages, 3 figure
Anomalous elasticity of cellular tissue vertex model
Vertex Models, as used to describe cellular tissue, have an energy controlled
by deviations of each cell area and perimeter from target values. The
constrained nonlinear relation between area and perimeter leads to new
mechanical response. Here we provide a mean-field treatment of a highly
simplified model: a uniform network of regular polygons with no topological
rearrangements. Since all polygons deform in the same way, we only need to
analyze the ground states and the response to deformations of a single polygon
(cell). The model exhibits the known transition between a fluid/compatible
state, where the cell can accommodate both target area and perimeter, and a
rigid/incompatible state. %The rigid solid-like state has a single gapped
ground state. We calculate and measure the mechanical resistance to various
deformation protocols and discover that at the onset of rigidity, where a
single zero-energy ground-state exists, %We show that in the incompatible
state, where a single frustrated ground-state exists, linear elasticity fails
to describe the mechanical response to even infinitesimal deformations. In
particular we identify a breakdown of reciprocity expressed via different
moduli for compressive and tensile loads, implying non-analyticity of the
energy functional. We give a pictorial representation in configuration space
that reveals that the complex elastic response of the Vertex Model arises from
the presence of two distinct sets of reference states (associated with target
area and target perimeter)
The role of non-affine deformations in the elastic behavior of the cellular vertex model
The vertex model of epithelia describes the apical surface of a tissue as a
tiling of polygonal cells, with a mechanical energy governed by deviations in
cell shape from preferred, or target, area, , and perimeter, . The
model exhibits a rigidity transition driven by geometric incompatibility as
tuned by the target shape index, . For , with the perimeter of a regular
hexagon of unit area, a cell can simultaneously attain both the preferred area
and preferred perimeter. As a result, the tissue is in a mechanically soft
compatible state, with zero shear and Young's moduli. For , it is
geometrically impossible for any cell to realize the preferred area and
perimeter simultaneously, and the tissue is in an incompatible rigid solid
state. Using a mean-field approach, we present a complete analytical
calculation of the linear elastic moduli of an ordered vertex model. We analyze
a relaxation step that includes non-affine deformations, leading to a softer
response than previously reported. The origin of the vanishing shear and
Young's moduli in the compatible state is the presence of zero-energy
deformations of cell shape. The bulk modulus exhibits a jump discontinuity at
the transition and can be lower in the rigid state than in the fluid-like
state. The Poisson's ratio can become negative which lowers the bulk and
Young's moduli. Our work provides a unified treatment of linear elasticity for
the vertex model and demonstrates that this linear response is
protocol-dependent
Cooperation of dual modes of cell motility promotes epithelial stress relaxation to accelerate wound healing
Collective cell migration in cohesive units is vital for tissue
morphogenesis, wound repair, and immune response. While the fundamental driving
forces for collective cell motion stem from contractile and protrusive
activities of individual cells, it remains unknown how their balance is
optimized to maintain tissue cohesiveness and the fluidity for motion. Here we
present a cell-based computational model for collective cell migration during
wound healing that incorporates mechanochemical coupling of cell motion and
adhesion kinetics with stochastic transformation of active motility forces. We
show that a balance of protrusive motility and actomyosin contractility is
optimized for accelerating the rate of wound repair, which is robust to
variations in cell and substrate mechanical properties. This balance underlies
rapid collective cell motion during wound healing, resulting from a tradeoff
between tension mediated collective cell guidance and active stress relaxation
in the tissue
A Novel Task for the Investigation of Action Acquisition
We present a behavioural task designed for the investigation of how novel instrumental actions are discovered and learnt. The task consists of free movement with a manipulandum, during which the full range of possible movements can be explored by the participant and recorded. A subset of these movements, the ‘target’, is set to trigger a reinforcing signal. The task is to discover what movements of the manipulandum evoke the reinforcement signal. Targets can be defined in spatial, temporal, or kinematic terms, can be a combination of these aspects, or can represent the concatenation of actions into a larger gesture. The task allows the study of how the specific elements of behaviour which cause the reinforcing signal are identified, refined and stored by the participant. The task provides a paradigm where the exploratory motive drives learning and as such we view it as in the tradition of Thorndike [1]. Most importantly it allows for repeated measures, since when a novel action is acquired the criterion for triggering reinforcement can be changed requiring a new action to be discovered. Here, we present data using both humans and rats as subjects, showing that our task is easily scalable in difficulty, adaptable across species, and produces a rich set of behavioural measures offering new and valuable insight into the action learning process
The Household Water Insecurity Experiences (HWISE) Scale: comparison scores from 27 sites in 22 countries
Abstract Household survey data from 27 sites in 22 countries were collected in 2017–2018 in order to construct and validate a cross-cultural household-level water insecurity scale. The resultant Household Water Insecurity Experiences (HWISE) scale presents a useful tool for monitoring and evaluating water interventions as a complement to traditional metrics used by the development community. It can also help track progress toward achievement of Sustainable Development Goal 6 ‘clean water and sanitation for all’. We present HWISE scale scores from 27 sites as comparative data for future studies using the HWISE scale in low- and middle-income contexts. Site-level mean scores for HWISE-12 (scored 0–36) ranged from 1.64 (SD 4.22) in Pune, India, to 20.90 (7.50) in Cartagena, Colombia, while site-level mean scores for HWISE-4 (scored 0–12) ranged from 0.51 (1.50) in Pune, India, to 8.21 (2.55) in Punjab, Pakistan. Scores tended to be higher in the dry season as expected. Data from this first implementation of the HWISE scale demonstrate the diversity of water insecurity within and across communities and can help to situate findings from future applications of this tool
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Pulsatile contractions and pattern formation in excitable actomyosin cortex
The actin cortex is an active adaptive material, embedded with complex regulatory networks that can sense, generate, and transmit mechanical forces. The cortex exhibits a wide range of dynamic behaviours, from generating pulsatory contractions and travelling waves to forming organised structures. Despite the progress in characterising the biochemical and mechanical components of the actin cortex, the emergent dynamics of this mechanochemical system is poorly understood. Here we develop a reaction-diffusion model for the RhoA signalling network, the upstream regulator for actomyosin assembly and contractility, coupled to an active actomyosin gel, to investigate how the interplay between chemical signalling and mechanical forces regulates stresses and patterns in the cortex. We demonstrate that mechanochemical feedback in the cortex acts to destabilise homogeneous states and robustly generate pulsatile contractions. By tuning active stress in the system, we show that the cortex can generate propagating contraction pulses, form network structures, or exhibit topological turbulence