Non-equilibrium microtubule fluctuations in a model cytoskeleton

Biological activity gives rise to non-equilibrium fluctuations in the cytoplasm of cells; however, there are few methods to directly measure these fluctuations. Using a reconstituted actin cytoskeleton, we show that the bending dynamics of embedded microtubules can be used to probe local stress fluctuations. We add myosin motors that drive the network out of equilibrium, resulting in an increased amplitude and modified time-dependence of microtubule bending fluctuations. We show that this behavior results from step-like forces on the order of 10 pN driven by collective motor dynamics

Theoretical Study of Fluid Membranes of Spherical Topology with Internal Degrees of Freedom

A theoretical study of vesicles of topological genus zero is presented. The bilayer membranes forming the vesicles have various degrees of intrinsic (tangent-plane) orientational order, ranging from smectic to hexatic, frustrated by curvature and topology. The field-theoretical model for these `$n$-atic' surfaces has been studied before in the low temperature (mean-field) limit. Work presented here includes the effects of thermal fluctuations. Using the lowest Landau level approximation, the coupling between order and shape is cast in a simple form, facilitating insights into the behaviour of vesicles. The order parameter contains vortices, whose effective interaction potential is found, and renormalized by membrane fluctuations. The shape of the phase space has a counter-intuitive influence on this potential. A criterion is established whereby a vesicle of finite rigidity may be burst by its own in-plane order, and an analogy is drawn with flux exclusion from a type-I superconductor.Comment: 34 pages + 4 Postscript figures. Uses RevTe

n-atic Order and Continuous Shape Changes of Deformable Surfaces of Genus Zero

We consider in mean-field theory the continuous development below a second-order phase transition of $n$-atic tangent plane order on a deformable surface of genus zero with order parameter $\psi = \langle e^{i n \theta} \rangle$. Tangent plane order expels Gaussian curvature. In addition, the total vorticity of orientational order on a surface of genus zero is two. Thus, the ordered phase of an $n$-atic on such a surface will have $2n$ vortices of strength $1/n$, $2n$ zeros in its order parameter, and a nonspherical equilibrium shape. Our calculations are based on a phenomenological model with a gauge-like coupling between $\psi$ and curvature, and our analysis follows closely the Abrikosov treatment of a type II superconductor just below $H_{c2}$.Comment: REVTEX, 12 page

Microtubules can bear enhanced compressive loads in living cells because of lateral reinforcement

Cytoskeletal microtubules have been proposed to influence cell shape and mechanics based on their ability to resist large-scale compressive forces exerted by the surrounding contractile cytoskeleton. Consistent with this, cytoplasmic microtubules are often highly curved and appear buckled because of compressive loads. However, the results of in vitro studies suggest that microtubules should buckle at much larger length scales, withstanding only exceedingly small compressive forces. This discrepancy calls into question the structural role of microtubules, and highlights our lack of quantitative knowledge of the magnitude of the forces they experience and can withstand in living cells. We show that intracellular microtubules do bear large-scale compressive loads from a variety of physiological forces, but their buckling wavelength is reduced significantly because of mechanical coupling to the surrounding elastic cytoskeleton. We quantitatively explain this behavior, and show that this coupling dramatically increases the compressive forces that microtubules can sustain, suggesting they can make a more significant structural contribution to the mechanical behavior of the cell than previously thought possible

The identification and management of depression in UK Kidney Care: Results from the Mood Maps Study

BACKGROUND: Depression is common in people with chronic kidney disease, yet little is known about how depression is identified and managed as part of routine kidney care. OBJECTIVES: The primary objective was to survey all UK adult kidney centres to understand how depression is identified and managed. A secondary objective was to broadly describe the variability in psychosocial care. DESIGN: Online survey. METHODS: The survey comprised of three sections: (1) general kidney care, (2) psychological provision and (3) social work provision. RESULTS: 48/68 (71%) of centres responded to the general survey with 20 and 13 responses from psychological and social work module respectively. Only 31.4% reported having both in centre psychological and social work practitioners. Three centres reported no access to psychosocial provision. Of the 25 centres who reported on pathways, 36.0% reported having internal pathways for the identification and management of depression. Within services with psychological provision, screening for depression varied across modality/group (e.g., 7.1% in mild/moderate chronic kidney disease vs. 62.5% in kidney donors). Cognitive Behavioural Therapy and Acceptance and Commitment Therapy were the most common interventions offered. Most psychosocial services were aware of the National Institute for Health and Care Excellence guidelines for managing depression in long-term conditions (n = 18, 94.7%) yet few fully utilised (n = 6, 33.3%). Limited workforce capacity was evident. CONCLUSIONS: There is considerable variability in approaches taken to identify and treat depression across UK kidney services, with few services having specific pathways designed to detect and manage depression. Workforce capacity remains a significant issue

The kinetics of antibody binding to Plasmodium falciparum VAR2CSA PfEMP1 antigen and modelling of PfEMP1 antigen packing on the membrane knobs

<p>Abstract</p> <p>Background</p> <p>Infected humans make protective antibody responses to the PfEMP1 adhesion antigens exported by <it>Plasmodium falciparum </it>parasites to the erythrocyte membrane, but little is known about the kinetics of this antibody-receptor binding reaction or how the topology of PfEMP1 on the parasitized erythrocyte membrane influences antibody association with, and dissociation from, its antigenic target.</p> <p>Methods</p> <p>A Quartz Crystal Microbalance biosensor was used to measure the association and dissociation kinetics of VAR2CSA PfEMP1 binding to human monoclonal antibodies. Immuno-fluorescence microscopy was used to visualize antibody-mediated adhesion between the surfaces of live infected erythrocytes and atomic force microscopy was used to obtain higher resolution images of the membrane knobs on the infected erythrocyte to estimate knob surface areas and model VAR2CSA packing density on the knob.</p> <p>Results</p> <p>Kinetic analysis indicates that antibody dissociation from the VAR2CSA PfEMP1 antigen is extremely slow when there is a high avidity interaction. High avidity binding to PfEMP1 antigens on the surface of <it>P. falciparum</it>-infected erythrocytes in turn requires bivalent cross-linking of epitopes positioned within the distance that can be bridged by antibody. Calculations of the surface area of the knobs and the possible densities of PfEMP1 packing on the knobs indicate that high-avidity cross-linking antibody reactions are constrained by the architecture of the knobs and the large size of PfEMP1 molecules.</p> <p>Conclusions</p> <p>High avidity is required to achieve the strongest binding to VAR2CSA PfEMP1, but the structures that display PfEMP1 also tend to inhibit cross-linking between PfEMP1 antigens, by holding many binding epitopes at distances beyond the 15-18 nm sweep radius of an antibody. The large size of PfEMP1 will also constrain intra-knob cross-linking interactions. This analysis indicates that effective vaccines targeting the parasite's vulnerable adhesion receptors should primarily induce strongly adhering, high avidity antibodies whose association rate constant is less important than their dissociation rate constant.</p