scholarly journals Cofilin Drives Rapid Turnover and Fluidization of Entangled F-actin

2017 ◽  
Author(s):  
Patrick M. McCall ◽  
Frederick C. MacKintosh ◽  
David R. Kovar ◽  
Margaret L. Gardel
Keyword(s):  
Steady State ◽  
Stress Relaxation ◽  
Actin Filaments ◽  
Atp Hydrolysis ◽  
Animal Cell ◽  
Animal Cells ◽  
Single Filament ◽  
Actin Cortex ◽  
Non Equilibrium ◽  
Entangled Solutions

AbstractThe shape of most animal cells is controlled by the actin cortex, a thin, isotropic network of dynamic actin filaments (F-actin) situated just beneath the plasma membrane. The cortex is held far from equilibrium by both active stresses and turnover: Myosin-II molecular motors drive deformations required for cell division, migration, and tissue morphogenesis, while turnover of the molecular components of the actin cortex relax stress and facilitate network reorganization. While many aspects of F-actin network viscoelasticity are well-characterized in the presence and absence of motor activity, a mechanistic understanding of how non-equilibrium actin turnover contributes to stress relaxation is still lacking. To address this, we developed a reconstituted in vitro system wherein the steady-state length and turnover rate of F-actin in entangled solutions are controlled by the actin regulatory proteins cofilin, profilin, and formin, which sever, recycle, and nucleate filaments, respectively. Cofilin-mediated severing accelerates the turnover and spatial reorganization of F-actin, without significant changes to filament length. Microrheology measurements demonstrate that cofilin-mediated severing is a single-timescale mode of stress relaxation that tunes the low-frequency viscosity over two orders of magnitude. These findings serve as the foundation for understanding the mechanics of more physiological F-actin networks with turnover, and inform an updated microscopic model of single-filament turnover. They also demonstrate that polymer activity, in the form of ATP hydrolysis on F-actin coupled to nucleotide-dependent cofilin binding, is sufficient to generate a form of active matter wherein asymmetric filament disassembly preserves filament number in spite of sustained severing.Significance StatementWhen an animal cell moves or divides, a disordered network of actin filaments (F-actin) plays a central role in controlling the resulting changes in cell shape. While it is known that continual turnover of F-actin by cofilin-mediated severing aids in reorganization of the cellular cytoskeleton, it is unclear how the turnover of structural elements alters the mechanical properties of the network. Here we show that severing of F-actin by cofilin results in a stress relaxation mechanism in entangled solutions characterized by a single-timescale set by the severing rate. Additionally, we identify ATP hydrolysis and nucleotide-dependent cofilin binding as sufficient ingredients to generate a non-equilibrium steady-state in which asymmetric F-actin disassembly preserves filament number in spite of sustained severing.

scholarly journals Cofilin drives rapid turnover and fluidization of entangled F-actin

2019 ◽  
Vol 116 (26) ◽  
pp. 12629-12637 ◽  
Author(s):  
Patrick M. McCall ◽  
Frederick C. MacKintosh ◽  
David R. Kovar ◽  
Margaret L. Gardel
Keyword(s):  
Stress Relaxation ◽  
Molecular Motors ◽  
Atp Hydrolysis ◽  
Low Frequency ◽  
Animal Cells ◽  
Single Filament ◽  
Actin Cortex ◽  
Spatial Reorganization ◽  
Actin Regulatory Proteins

The shape of most animal cells is controlled by the actin cortex, a thin network of dynamic actin filaments (F-actin) situated just beneath the plasma membrane. The cortex is held far from equilibrium by both active stresses and polymer turnover: Molecular motors drive deformations required for cell morphogenesis, while actin-filament disassembly dynamics relax stress and facilitate cortical remodeling. While many aspects of actin-cortex mechanics are well characterized, a mechanistic understanding of how nonequilibrium actin turnover contributes to stress relaxation is still lacking. To address this, we developed a reconstituted in vitro system of entangled F-actin, wherein the steady-state length and turnover rate of F-actin are controlled by the actin regulatory proteins cofilin, profilin, and formin, which sever, recycle, and assemble filaments, respectively. Cofilin-mediated severing accelerates the turnover and spatial reorganization of F-actin, without significant changes to filament length. We demonstrate that cofilin-mediated severing is a single-timescale mode of stress relaxation that tunes the low-frequency viscosity over two orders of magnitude. These findings serve as the foundation for understanding the mechanics of more physiological F-actin networks with turnover and inform an updated microscopic model of single-filament turnover. They also demonstrate that polymer activity, in the form of ATP hydrolysis on F-actin coupled to nucleotide-dependent cofilin binding, is sufficient to generate a form of active matter wherein asymmetric filament disassembly preserves filament number despite sustained severing.

scholarly journals Actin kinetics shapes cortical network structure and mechanics

2016 ◽  
Vol 2 (4) ◽  
pp. e1501337 ◽  
Author(s):  
Marco Fritzsche ◽  
Christoph Erlenkämper ◽  
Emad Moeendarbary ◽  
Guillaume Charras ◽  
Karsten Kruse
Keyword(s):  
Single Molecule ◽  
Actin Filaments ◽  
Length Distribution ◽  
Living Cells ◽  
Stochastic Simulations ◽  
Cortical Actin ◽  
Animal Cells ◽  
Cellular Mechanics ◽  
Cellular Processes ◽  
Actin Cortex

The actin cortex of animal cells is the main determinant of cellular mechanics. The continuous turnover of cortical actin filaments enables cells to quickly respond to stimuli. Recent work has shown that most of the cortical actin is generated by only two actin nucleators, the Arp2/3 complex and the formin Diaph1. However, our understanding of their interplay, their kinetics, and the length distribution of the filaments that they nucleate within living cells is poor. Such knowledge is necessary for a thorough comprehension of cellular processes and cell mechanics from basic polymer physics principles. We determined cortical assembly rates in living cells by using single-molecule fluorescence imaging in combination with stochastic simulations. We find that formin-nucleated filaments are, on average, 10 times longer than Arp2/3-nucleated filaments. Although formin-generated filaments represent less than 10% of all actin filaments, mechanical measurements indicate that they are important determinants of cortical elasticity. Tuning the activity of actin nucleators to alter filament length distribution may thus be a mechanism allowing cells to adjust their macroscopic mechanical properties to their physiological needs.

Supradegeneracy and the Second Law of Thermodynamics

2020 ◽  
Vol 45 (2) ◽  
pp. 121-132
Author(s):  
Daniel P. Sheehan
Keyword(s):  
Steady State ◽  
Statistical Mechanics ◽  
Population Inversion ◽  
Laboratory Experiments ◽  
Second Law Of Thermodynamics ◽  
Second Law ◽  
Boltzmann Factor ◽  
Energy Currents ◽  
Non Equilibrium

AbstractCanonical statistical mechanics hinges on two quantities, i. e., state degeneracy and the Boltzmann factor, the latter of which usually dominates thermodynamic behaviors. A recently identified phenomenon (supradegeneracy) reverses this order of dominance and predicts effects for equilibrium that are normally associated with non-equilibrium, including population inversion and steady-state particle and energy currents. This study examines two thermodynamic paradoxes that arise from supradegeneracy and proposes laboratory experiments by which they might be resolved.

scholarly journals Modules or Mean-Fields?

Entropy ◽  
2020 ◽  
Vol 22 (5) ◽  
pp. 552 ◽  
Author(s):  
Thomas Parr ◽  
Noor Sajid ◽  
Karl J. Friston
Keyword(s):  
Steady State ◽  
Message Passing ◽  
Mean Field Theory ◽  
Functional Anatomy ◽  
Mean Field ◽  
State Density ◽  
Stochastic Dynamical Systems ◽  
Conditional Independency ◽  
The Brain ◽  
Non Equilibrium

The segregation of neural processing into distinct streams has been interpreted by some as evidence in favour of a modular view of brain function. This implies a set of specialised ‘modules’, each of which performs a specific kind of computation in isolation of other brain systems, before sharing the result of this operation with other modules. In light of a modern understanding of stochastic non-equilibrium systems, like the brain, a simpler and more parsimonious explanation presents itself. Formulating the evolution of a non-equilibrium steady state system in terms of its density dynamics reveals that such systems appear on average to perform a gradient ascent on their steady state density. If this steady state implies a sufficiently sparse conditional independency structure, this endorses a mean-field dynamical formulation. This decomposes the density over all states in a system into the product of marginal probabilities for those states. This factorisation lends the system a modular appearance, in the sense that we can interpret the dynamics of each factor independently. However, the argument here is that it is factorisation, as opposed to modularisation, that gives rise to the functional anatomy of the brain or, indeed, any sentient system. In the following, we briefly overview mean-field theory and its applications to stochastic dynamical systems. We then unpack the consequences of this factorisation through simple numerical simulations and highlight the implications for neuronal message passing and the computational architecture of sentience.

scholarly journals Mechanism of the formation of contractile ring in dividing cultured animal cells. II. Cortical movement of microinjected actin filaments.

1990 ◽  
Vol 111 (5) ◽  
pp. 1905-1911 ◽  
Author(s):  
L G Cao ◽  
Y L Wang
Keyword(s):  
Actin Filaments ◽  
Average Rate ◽  
Rat Kidney ◽  
Equatorial Region ◽  
Cell Cortex ◽  
Polar Regions ◽  
Cortical Actin ◽  
Animal Cells ◽  
Contractile Ring ◽  
Directional Movement

The contractile ring in dividing animal cells is formed primarily through the reorganization of existing actin filaments (Cao, L.-G., and Y.-L. Wang. 1990. J. Cell Biol. 110:1089-1096), but it is not clear whether the process involves a random recruitment of diffusible actin filaments from the cytoplasm, or a directional movement of cortically associated filaments toward the equator. We have studied this question by observing the distribution of actin filaments that have been labeled with fluorescent phalloidin and microinjected into dividing normal rat kidney (NRK) cells. The labeled filaments are present primarily in the cytoplasm during prometaphase and early metaphase, but become associated extensively with the cell cortex 10-15 min before the onset of anaphase. This process is manifested both as an increase in cortical fluorescence intensity and as movements of discrete aggregates of actin filaments toward the cortex. The concentration of actin fluorescence in the equatorial region, accompanied by a decrease of fluorescence in polar regions, is detected 2-3 min after the onset of anaphase. By directly tracing the distribution of aggregates of labeled actin filaments, we are able to detect, during anaphase and telophase, movements of cortical actin filaments toward the equator at an average rate of 1.0 micron/min. Our results, combined with previous observations, suggest that the organization of actin filaments during cytokinesis probably involves an association of cytoplasmic filaments with the cortex, a movement of cortical filaments toward the cleavage furrow, and a dissociation of filaments from the equatorial cortex.

scholarly journals Lifshitz hydrodynamics at generic z from a moving black brane

2021 ◽  
Vol 2021 (7) ◽  
Author(s):  
Aruna Rajagopal ◽  
Larus Thorlacius
Keyword(s):  
Field Theory ◽  
Steady State ◽  
Critical Exponent ◽  
Stress Tensor ◽  
Perfect Fluid ◽  
Scale Invariance ◽  
Linear Momentum ◽  
Black Brane ◽  
Dilaton Gravity ◽  
Non Equilibrium

Abstract A Lifshitz black brane at generic dynamical critical exponent z > 1, with non-zero linear momentum along the boundary, provides a holographic dual description of a non-equilibrium steady state in a quantum critical fluid, with Lifshitz scale invariance but without boost symmetry. We consider moving Lifshitz branes in Einstein-Maxwell-Dilaton gravity and obtain the non-relativistic stress tensor complex of the dual field theory via a suitable holographic renormalisation procedure. The resulting black brane hydrodynamics and thermodynamics are a concrete holographic realization of a Lifshitz perfect fluid with a generic dynamical critical exponent.

Thermal Diffusivity of the Mott Insulator Ca2RuO4 in a Non-equilibrium Steady State

2021 ◽  
Vol 90 (6) ◽  
pp. 063601
Author(s):  
Shuji Kawasaki ◽  
Akitoshi Nakano ◽  
Hiroki Taniguchi ◽  
Hai Jun Cho ◽  
Hiromichi Ohta ◽  
...  
Keyword(s):  
Steady State ◽  
Thermal Diffusivity ◽  
Mott Insulator ◽  
Non Equilibrium

Stress mRNA metabolism in canavanine-treated chicken embryo cells

1984 ◽  
Vol 4 (8) ◽  
pp. 1534-1541
Author(s):  
C N White ◽  
L E Hightower
Keyword(s):  
Steady State ◽  
Stress Proteins ◽  
Animal Cell ◽  
Stress Protein ◽  
High Rate ◽  
Rrna Synthesis ◽  
28S Rrna ◽  
Mrna Levels ◽  
Molecular Weights

Four major chicken stress mRNAs with apparent molecular weights of 1.2 X 10(6), 0.88 X 10(6), 0.59 X 10(6), and 0.25 X 10(6) to 0.28 X 10(6) were separated on acidic agarose-urea gels. Using cell-free translation, the coding assignments of these mRNAs were determined to be stress proteins with apparent molecular weights of 88,000, 71,000, 35,000, and 23,000. Despite high levels of translational activity in vivo and in vitro, no newly synthesized mRNA for the 23-kilodalton stress protein was detected on gels under conditions which readily allowed detection of other stress mRNAs, suggesting activation of a stored or incompletely processed mRNA. Cloned Drosophila heat shock genes were used to identify and measure changes in cellular levels of the two largest stress mRNAs. Synthesis of these mRNAs increased rapidly during the first hour of canavanine treatment and continued at a high rate for at least 7 h, with the mRNAs attaining new steady-state levels by ca. 3 h. Both of these inducible stress mRNAs had very short half-lives compared with other animal cell mRNAs. Using an approach-to-steady-state analysis, the half-lives were calculated to be 89 min for the mRNA encoding the 88-kilodalton stress protein and 46 min for the mRNA encoding the 71-kilodalton stress protein. Chicken 18S and 28S rRNA synthesis was inhibited, and actin mRNA levels measured with cloned cDNA encoding chicken beta-actin slowly declined in canavanine-treated cells.

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