2,046 research outputs found
Filling Gaps in Signaling to Actin Cytoskeletal Remodeling
AbstractA recent publication in the April 4 issue of Cell advances our understanding of stimulus response coupling leading to actin remodeling. It describes the identification of a novel membrane component Mig-2 that engages filamin A through a new intermediary, migfilin, to stimulate actin assembly and cell spreading on a substrate of extracellular matrix
Nonlinear elasticity of stiff biopolymers connected by flexible linkers
Networks of the biopolymer actin, cross-linked by the compliant protein filamin, form soft gels. They can, however, withstand large shear stresses due to their pronounced nonlinear elastic behavior. The nonlinear elasticity can be controlled by varying the number of cross-links per actin filament. We propose and test a model of rigid filaments decorated by multiple flexible linkers that is in quantitative agreement with experiment. This allows us to estimate loads on individual cross-links, which we find to be less than 10 pN. © 2009 The American Physical Society
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The Influence of Social Dependencies on Decision-Making: Initial Investigations with a New Game
This paper describes a new multi-player computer game, Colored Trails (CT), which may be played by people, computers and heterogeneous groups. CT was designed to enable investigation of properties of decision-making strategies in multi-agent situations of varying complexity. The paper presents the results of an initial series of experiments of CT games in which agents' choices affected not only their own outcomes but also the outcomes of other agents. It compares the behavior of people with that of computer agents deploying a variety of decision-making strategies. The results align with behavioral economics studies in showing that people cooperate when they play and that factors of social dependency influence their levels of cooperation. Preliminary results indicate that people design agents to play strategies closer to game-theory predictions, yielding lower utility. Additional experiments show that such agents perform worse than agents designed to make choices that resemble human cooperative behavior. The paper describes challenges raised by these results for designers of agents, especially agents that need to operate in heterogeneous groups that include people.Engineering and Applied Science
On the form of growing strings
Patterns and forms adopted by Nature, such as the shape of living cells, the
geometry of shells and the branched structure of plants, are often the result
of simple dynamical paradigms. Here we show that a growing self-interacting
string attached to a tracking origin, modeled to resemble nascent polypeptides
in vivo, develops helical structures which are more pronounced at the growing
end. We also show that the dynamic growth ensemble shares several features of
an equilibrium ensemble in which the growing end of the polymer is under an
effective stretching force. A statistical analysis of native states of proteins
shows that the signature of this non-equilibrium phenomenon has been fixed by
evolution at the C-terminus, the growing end of a nascent protein. These
findings suggest that a generic non-equilibrium growth process might have
provided an additional evolutionary advantage for nascent proteins by favoring
the preferential selection of helical structures.Comment: 4 pages, 3 figures. Accepted for publication in Phys. Rev. Let
Decreased levels of the gelsolin plasma isoform in patients with rheumatoid arthritis
Introduction Gelsolin is an intracellular actin-binding protein involved in cell shape changes, cell motility, and apoptosis. An extracellular gelsolin isoform, plasma gelsolin circulates in the blood of healthy individuals at a concentration of mg/L and has been suggested to be a key component of an extracellular actin-scavenging system during tissue damage. Levels of plasma gelsolin decrease during acute injury and inflammation, and administration of recombinant plasma gelsolin to animals improves outcomes following sepsis or burn injuries. In the present study, we investigated plasma gelsolin in patients with rheumatoid arthritis.Methods Circulating and intra-articular levels of plasma gelsolin were measured in 78 patients with rheumatoid arthritis using a functional (pyrene-actin nucleation) assay and compared with 62 age- and gender-matched healthy controls.Results Circulating plasma gelsolin levels were significantly lower in patients with rheumatoid arthritis compared with healthy controls ( versus mg/L, P = 0.0002). The patients' intra-articular plasma gelsolin levels were significantly lower than in the paired plasma samples ( versus mg/L, P = 0.0001). Actin was detected in the synovial fluids of all but four of the patients, and immunoprecipitation experiments identified gelsolin-actin complexes.Conclusions The plasma isoform of gelsolin is decreased in the plasma of patients with rheumatoid arthritis compared with healthy controls. The reduced plasma concentrations in combination with the presence of actin and gelsolin-actin complexes in synovial fluids suggest a local consumption of this potentially anti-inflammatory protein in the inflamed joint
Dynamic Phase Transitions in Cell Spreading
We monitored isotropic spreading of mouse embryonic fibroblasts on
fibronectin-coated substrates. Cell adhesion area versus time was measured via
total internal reflection fluorescence microscopy. Spreading proceeds in
well-defined phases. We found a power-law area growth with distinct exponents
a_i in three sequential phases, which we denote basal (a_1=0.4+-0.2), continous
(a_2=1.6+-0.9) and contractile (a_3=0.3+-0.2) spreading. High resolution
differential interference contrast microscopy was used to characterize local
membrane dynamics at the spreading front. Fourier power spectra of membrane
velocity reveal the sudden development of periodic membrane retractions at the
transition from continous to contractile spreading. We propose that the
classification of cell spreading into phases with distinct functional
characteristics and protein activity patterns serves as a paradigm for a
general program of a phase classification of cellular phenotype. Biological
variability is drastically reduced when only the corresponding phases are used
for comparison across species/different cell lines.Comment: 4 pages, 5 figure
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Mechanical Perturbation of Filamin A Immunoglobulin Repeats 20-21 Reveals Potential Non-equilibrium Mechanochemical Partner Binding Function
The actin crosslinking protein filamin A (FLNa) mediates mechanotransduction, a conversion of mechanical forces into cellular biochemical signals to regulate cell growth and survival. To provide more quantitative insight into this process, we report results using magnetic tweezers that relate mechanical force to conformational changes of FLNa immunoglobulin-like repeats (IgFLNa) 20–21, previously identified as a mechanosensing domain. We determined the force magnitudes required to unfold previously identified structural organizations of the β-strands in the two domains: IgFLNa 20 unfolds at ~15 pN and IgFLNa 21 unfolding requires significantly larger forces. Unfolded domain IgFLNa 20 can exist in two different conformational states, which lead to different refolding kinetics of the IgFLNa 20 and imply a significant impact on the reformation of the domain pair at reduced force values. We discuss the relevance of the findings to force bearing and mechanosensing functions of FLNa
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