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

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

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

Stress-Dependent Elasticity of Composite Actin Networks as a Model for Cell Behavior

Networks of filamentous actin cross-linked with the actin-binding protein filamin A exhibit remarkable strain stiffening leading to an increase in differential elastic modulus by several orders of magnitude over the linear value. The variation of the frequency dependence of the differential elastic and loss moduli as a function of prestress is consistent with that observed in living cells, suggesting that cell elasticity is always measured in the nonlinear regime, and that prestress is an essential control parameter

Self-organized Vortex State in Two-dimensional Dictyostelium Dynamics

We present results of experiments on the dynamics of Dictyostelium discoideum in a novel set-up which constraints cell motion to a plane. After aggregation, the amoebae collect into round ''pancake" structures in which the cells rotate around the center of the pancake. This vortex state persists for many hours and we have explicitly verified that the motion is not due to rotating waves of cAMP. To provide an alternative mechanism for the self-organization of the Dictyostelium cells, we have developed a new model of the dynamics of self-propelled deformable objects. In this model, we show that cohesive energy between the cells, together with a coupling between the self-generated propulsive force and the cell's configuration produces a self-organized vortex state. The angular velocity profiles of the experiment and of the model are qualitatively similar. The mechanism for self-organization reported here can possibly explain similar vortex states in other biological systems.Comment: submitted to PRL; revised version dated 3/8/9

Hypothesis: are neoplastic macrophages/microglia present in glioblastoma multiforme?

Most malignant brain tumours contain various numbers of cells with characteristics of activated or dysmorphic macrophages/microglia. These cells are generally considered part of the tumour stroma and are often described as TAM (tumour-associated macrophages). These types of cells are thought to either enhance or inhibit brain tumour progression. Recent evidence indicates that neoplastic cells with macrophage characteristics are found in numerous metastatic cancers of non-CNS (central nervous system) origin. Evidence is presented here suggesting that subpopulations of cells within human gliomas, specifically GBM (glioblastoma multiforme), are neoplastic macrophages/microglia. These cells are thought to arise following mitochondrial damage in fusion hybrids between neoplastic stem cells and macrophages/microglia