162 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
The stoichiometry of P2X2/6 receptor heteromers depends on relative subunit expression levels
Fast synaptic transmission involves the operation of ionotropic receptors, which are often composed of at least two types of subunit. We have developed a method, based on atomic force microscopy imaging to determine the stoichiometry and subunit arrangement within ionotropic receptors. We showed recently that the P2X(2) receptor for ATP is expressed as a trimer but that the P2X(6) subunit is unable to oligomerize. In this study we addressed the subunit stoichiometry of heteromers containing both P2X(2) and P2X(6) subunits. We transfected tsA 201 cells with both P2X(2) and P2X(6) subunits, bearing different epitope tags. We manipulated the transfection conditions so that either P2X(2) or P2X(6) was the predominant subunit expressed. By atomic force microscopy imaging of isolated receptors decorated with antiepitope antibodies, we demonstrate that when expression of the P2X(2) subunit predominates, the receptors contain primarily 2 x P2X(2) subunits and 1 x P2X(6) subunit. In contrast, when the P2X(6) subunit predominates, the subunit stoichiometry of the receptors is reversed. Our results show that the composition of P2X receptor heteromers is plastic and dependent on the relative subunit expression levels. We suggest that this property of receptor assembly might introduce an additional layer of subtlety into P2X receptor signaling
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
AFM imaging reveals the assembly of a P2X receptor complex containing P2X2, P2X4 and P2X6 subunits
Seven P2X purinergic receptor subunits have been identified: P2X1-P2X7. All except P2X6 assemble as homotrimers, and six heteromeric receptors (P2X1/2, P2X1/4, P2X1/5, P2X2/3, P2X2/6 and P2X4/6) have been described. In addition, P2X4 homomers associate with P2X2 or P2X7 homomers as dimers of trimers. The various P2X receptors show individual functional properties, suggesting distinct physiological roles. The overlapping expression of P2X2, P2X4 and P2X6 subunits has been shown in different cell types, and functional analysis of P2X receptors in Leydig cells suggests that the three subunits interact
Growing Multiconfigurational Potential Energy Surfaces with Applications to X+H2 (X=C,N,O) Reactions
A previously developed method, based on a Shepard interpolation procedure to automatically construct a quantum mechanical potential energy surface (PES), is extended to the construction of multiple potential energy surfaces using multiconfigurational wave functions. These calculations are accomplished with the interface of the PES-building program, GROW, and the GAMESS suite of electronic structure programs. The efficient computation of multiconfigurational self-consistent field surfaces is illustrated with the C+H2, N+H2, and O+H2reactions
Entropy Production Rate is Maximized in Non-Contractile Actomyosin
The actin cytoskeleton is an active semi-flexible polymer network whose
non-equilibrium properties coordinate both stable and contractile behaviors to
maintain or change cell shape. While myosin motors drive the actin cytoskeleton
out-of-equilibrium, the role of myosin-driven active stresses in the
accumulation and dissipation of mechanical energy is unclear. To investigate
this, we synthesize an actomyosin material in vitro whose active stress content
can tune the network from stable to contractile. Each increment in activity
determines a characteristic spectrum of actin filament fluctuations which is
used to calculate the total mechanical work and the production of entropy in
the material. We find that the balance of work and entropy does not increase
monotonically and, surprisingly, the entropy production rate is maximized in
the non-contractile, stable state. Our study provides evidence that the origins
of system entropy production and activity-dependent dissipation arise from
disorder in the molecular interactions between actin and myosinComment: 31 pages, 5 figure
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