Active Gel Model of Amoeboid Cell Motility

We develop a model of amoeboid cell motility based on active gel theory. Modeling the motile apparatus of a eukaryotic cell as a confined layer of finite length of poroelastic active gel permeated by a solvent, we first show that, due to active stress and gel turnover, an initially static and homogeneous layer can undergo a contractile-type instability to a polarized moving state in which the rear is enriched in gel polymer. This agrees qualitatively with motile cells containing an actomyosin-rich uropod at their rear. We find that the gel layer settles into a steadily moving, inhomogeneous state at long times, sustained by a balance between contractility and filament turnover. In addition, our model predicts an optimal value of the gel-susbstrate adhesion leading to maximum layer speed, in agreement with cell motility assays. The model may be relevant to motility of cells translocating in complex, confining environments that can be mimicked experimentally by cell migration through microchannels.Comment: To appear in New Journal of Physic

Multisensory Integration Sites Identified by Perception of Spatial Wavelet Filtered Visual Speech Gesture Information

Perception of speech is improved when presentation of the audio signal is accompanied by concordant visual speech gesture information. This enhancement is most prevalent when the audio signal is degraded. One potential means by which the brain affords perceptual enhancement is thought to be through the integration of concordant information from multiple sensory channels in a common site of convergence, multisensory integration (MSI) sites. Some studies have identified potential sites in the superior temporal gyrus/sulcus (STG/S) that are responsive to multisensory information from the auditory speech signal and visual speech movement. One limitation of these studies is that they do not control for activity resulting from attentional modulation cued by such things as visual information signaling the onsets and offsets of the acoustic speech signal, as well as activity resulting from MSI of properties of the auditory speech signal with aspects of gross visual motion that are not specific to place of articulation information. This fMRI experiment uses spatial wavelet bandpass filtered Japanese sentences presented with background multispeaker audio noise to discern brain activity reflecting MSI induced by auditory and visual correspondence of place of articulation information that controls for activity resulting from the above-mentioned factors. The experiment consists of a low-frequency (LF) filtered condition containing gross visual motion of the lips, jaw, and head without specific place of articulation information, a midfrequency (MF) filtered condition containing place of articulation information, and an unfiltered (UF) condition. Sites of MSI selectively induced by auditory and visual correspondence of place of articulation information were determined by the presence of activity for both the MF and UF conditions relative to the LF condition. Based on these criteria, sites of MSI were found predominantly in the left middle temporal gyrus (MTG), and the left STG/S (including the auditory cortex). By controlling for additional factors that could also induce greater activity resulting from visual motion information, this study identifies potential MSI sites that we believe are involved with improved speech perception intelligibility

Nematic cells with defect-patterned alignment layers

Using Monte Carlo simulations of the Lebwohl--Lasher model we study the director ordering in a nematic cell where the top and bottom surfaces are patterned with a lattice of $\pm 1$ point topological defects of lattice spacing $a$. We find that the nematic order depends crucially on the ratio of the height of the cell $H$ to $a$. When $H/a \gtrsim 0.9$ the system is very well--ordered and the frustration induced by the lattice of defects is relieved by a network of half--integer defect lines which emerge from the point defects and hug the top and bottom surfaces of the cell. When $H/a \lesssim 0.9$ the system is disordered and the half--integer defect lines thread through the cell joining point defects on the top and bottom surfaces. We present a simple physical argument in terms of the length of the defect lines to explain these results. To facilitate eventual comparison with experimental systems we also simulate optical textures and study the switching behavior in the presence of an electric field

Theory of nematic and polar active fluid surfaces

We derive a fully covariant theory of the hydrodynamics of nematic and polar active surfaces, subjected to internal and external forces and torques. We study the symmetries of polar and nematic surfaces and find that in addition to five different types of in-plane isotropic surfaces, polar and nematic surfaces can be classified into five polar, two pseudopolar, five nematic and two pseudonematic types of surfaces. We give examples of physical realisations of the different types of surfaces we have identified. We obtain expressions for the equilibrium tensions, moments, and external forces and torques acting on a passive polar or nematic surface. We calculate the entropy production rate using the framework of thermodynamics close to equilibrium and find constitutive equations for polar and nematic active surfaces with different symmetries. We study the instabilities of a confined flat planar-chiral polar active layer and of a confined deformable polar active surface with broken up-down symmetry

Oligoclonal expansions of CD8(+) T cells in chronic HIV infection are antigen specific

Acute HIV infection is associated with a vigorous immune response characterized by the proliferation of selected T cell receptor V beta (BV)-expressing CD8(+) T cells. These 'expansions', which are commonly detected in the peripheral blood, can persist during chronic HIV infection and may result in the dominance of particular clones. Such clonal populations are most consistent with antigen-driven expansions of CD8(+) T cells. However, due to the difficulties in studying antigen-specific T cells in vivo, it has been hard to prove that oligoclonal BV expansions are actually HIV specific. The use of tetrameric major histocompatibility complex-peptide complexes has recently enabled direct visualization of antigen-specific T cells ex vivo but has not provided information on their clonal composition. We have now made use of these tetrameric complexes in conjunction with anti-BV chain-specific monoclonal antibodies and analysis of cytotoxic T lymphocyte lines/clones to show that chronically clonally expanded CD8(+) T cells are HIV specific in vivo

Untwisting of a Strained Cholesteric Elastomer by Disclination Loop Nucleation

The application of a sufficiently strong strain perpendicular to the pitch axis of a monodomain cholesteric elastomer unwinds the cholesteric helix. Previous theoretical analyses of this transition ignored the effects of Frank elasticity which we include here. We find that the strain needed to unwind the helix is reduced because of the Frank penalty and the cholesteric state becomes metastable above the transition. We consider in detail a previously proposed mechanism by which the topologically stable helical texture is removed in the metastable state, namely by the nucleation of twist disclination loops in the plane perpendicular to the pitch axis. We present an approximate calculation of the barrier energy for this nucleation process which neglects possible spatial variation of the strain fields in the elastomer, as well as a more accurate calculation based on a finite element modeling of the elastomer.Comment: 12 pages, 9 figure

Contraction of cross-linked actomyosin bundles

Cross-linked actomyosin bundles retract when severed in vivo by laser ablation, or when isolated from the cell and micromanipulated in vitro in the presence of ATP. We identify the time scale for contraction as a viscoelastic time tau, where the viscosity is due to (internal) protein friction. We obtain an estimate of the order of magnitude of the contraction time tau ~ 10-100 s, consistent with available experimental data for circumferential microfilament bundles and stress fibers. Our results are supported by an exactly solvable, hydrodynamic model of a retracting bundle as a cylinder of isotropic, active matter, from which the order of magnitude of the active stress is estimated.Comment: To be published in Physical Biolog

Getting “Just Deserts” or Seeing the “Silver Lining”: The Relation between Judgments of Immanent and Ultimate Justice

People can perceive misfortunes as caused by previous bad deeds (immanent justice reasoning) or resulting in ultimate compensation (ultimate justice reasoning). Across two studies, we investigated the relation between these types of justice reasoning and identified the processes (perceptions of deservingness) that underlie them for both others (Study 1) and the self (Study 2). Study 1 demonstrated that observers engaged in more ultimate (vs. immanent) justice reasoning for a "good" victim and greater immanent (vs. ultimate) justice reasoning for a "bad" victim. In Study 2, participants' construals of their bad breaks varied as a function of their self-worth, with greater ultimate (immanent) justice reasoning for participants with higher (lower) self-esteem. Across both studies, perceived deservingness of bad breaks or perceived deservingness of ultimate compensation mediated immanent and ultimate justice reasoning respectively. © 2014 Harvey and Callan

Confinement and Low Adhesion Induce Fast Amoeboid Migration of Slow Mesenchymal Cells

The mesenchymal-amoeboid transition (MAT) was proposed as a mechanism for cancer cells to adapt their migration mode to their environment. While the molecular pathways involved in this transition are well documented, the role of the microenvironment in the MAT is still poorly understood. Here, we investigated how confinement and adhesion affect this transition. We report that, in the absence of focal adhesions and under conditions of confinement, mesenchymal cells can spontaneously switch to a fast amoeboid migration phenotype. We identified two main types of fast migration-one involving a local protrusion and a second involving a myosin-II-dependent mechanical instability of the cell cortex that leads to a global cortical flow. Interestingly, transformed cells are more prone to adopt this fast migration mode. Finally, we propose a generic model that explains migration transitions and predicts a phase diagram of migration phenotypes based on three main control parameters: confinement, adhesion, and contractility