Deformation-Enhanced Fluctuations in the Red Cell Skeleton with Theoretical Relations to Elasticity, Connectivity, and Spectrin Unfolding

To assess local elasticity in the red cell’s spectrin-actin network, nano-particles were tethered to actin nodes and their constrained thermal motions were tracked. Cells were both immobilized and controllably deformed by aspiration into a micropipette. Since the network is well-appreciated as soft, thermal fluctuations even in an unstressed portion of network were expected to be many tens of nanometers based on simple equipartition ideas. Real-time particle tracking indeed reveals such root-mean-squared motions for 40-nm fluorescent beads either tethered to actin directly within a cell ghost or connected to actin from outside a cell via glycophorin. Moreover, the elastically constrained displacements are significant on the scale of the network’s internodal distance of ~60-80 nm. Surprisingly, along the aspirated projection—where the network is axially extended by as much as twofold or more—fluctuations in the axial direction are increased by almost twofold relative to motions in the unstressed network. The molecular basis for such strain softening is discussed broadly in terms of force-driven transitions. Specific considerations are given to 1) protein dissociations that reduce network connectivity, and 2) unfolding kinetics of a localized few of the red cell’s ~107 spectrin repeats

Graphene-protein bioelectronic devices with wavelength-dependent photoresponse

We implemented a nanoelectronic interface between graphene field effect transistors (FETs) and soluble proteins. This enables production of bioelectronic devices that combine functionalities of the biomolecular and inorganic components. The method serves to link polyhistidine-tagged proteins to graphene FETs using the tag itself. Atomic Force Microscopy and Raman spectroscopy provide structural understanding of the bio/nano hybrid; current-gate voltage measurements are used to elucidate the electronic properties. As an example application, we functionalize graphene FETs with fluorescent proteins to yield hybrids that respond to light at wavelengths defined by the optical absorption spectrum of the proteinComment: 10 pages, 3 figures; To appear in Applied Physics Letter

Micelles of Different Morphologies - Advantages of Worm-like Filomicelles of PEO-PCL in Paclitaxel Delivery

Worm-like and spherical micelles are both prepared here from the same amphiphilic diblock copolymer, poly(ethylene oxide)-b-poly (ε-caprolactone) (PEO [5 kDa]-PCL [6.5 kDa]) in order to compare loading and delivery of hydrophobic drugs. Worm-like micelles of this degradable copolymer are nanometers in cross-section and spontaneously assemble to stable lengths of microns, resembling filoviruses in some respects and thus suggesting the moniker filomicelles . The highly flexible worm-like micelles can also be sonicated to generate kinetically stable spherical micelles composed of the same copolymer. The fission process exploits the finding that the PCL cores are fluid, rather than glassy or crystalline, and core-loading of the hydrophobic anticancer drug delivery, paclitaxel (TAX) shows that the worm-like micelles load and solubilize twice as much drug as spherical micelles. In cytotoxicity tests that compare to the clinically prevalent solubilizer, Cremophor® EL, both micellar carriers are far less toxic, and both types of TAX-loaded micelles also show 5-fold greater anticancer activity on A549 human lung cancer cells. PEO-PCL based worm-like filomicelles appear to be promising pharmaceutical nanocarriers with improved solubilization efficiency and comparable stability to spherical micelles, as well as better safety and efficacy in vitro compared to the prevalent Cremophor® EL TAX formulation

Stress and streets: How the network structure of streets is associated with stress-related brain activation

Previous research has examined the relation between urban design factors and mental health, but the impact of street networks is underrepresented. This exploratory, cross-sectional study examines the association between street network variables based on the Space Syntax theory and whole-brain activation during a social stress paradigm. Forty-two individuals who lived in Berlin participated in an fMRI study during which acute social stress was induced. Saliva cortisol concentrations, subjective stress ratings, and mean heart rate were assessed as proxies for a successful stress induction. Space Syntax was used as a tool to objectively measure street network characteristics including global integration (‘proximity’ of a street to all the other streets in a network), local integration (‘proximity’ of a street to a certain number of streets within a walkable area), connectivity (‘direct street connections’ a street has), and normalized angular choice (NACH) (‘straightest and shortest’ route for a street in a street network). They were analyzed within a 1500 m radius of participants' address (i.e., neighborhood) as well as for the street closest to their address (i.e., point address). Higher mean neighborhood global and local integration, which equate to better integrated streets in the network, were associated with less activation during stress provocation in several brain regions, including dorsal anterior cingulate cortex, insula, and thalamus, which play a role in the detection of salient stimuli and threats. No association was found between brain activity and global and local integration for the point address. There was also no association between brain activity and connectivity or NACH for any conditions. The study indicates that Space Syntax is a useful tool for measuring macro-scale urban space (e.g., street networks) in neuro-urbanistic studies. The results underline the need to explore the potential of optimizing street networks to better understand pathways to urban mental health.</p

Curvature-driven Molecular Demixing in the Budding and Breakup of Mixed Component Worm-like Miscelles

Amphiphilic block copolymers of suitable proportions can self-assemble into surprisingly long and stable worm-like micelles, but the intrinsic polydispersity of polymers as well as polymer blending efforts and the increasing use of degradable chains all raise basic questions of curvature–composition coupling and morphological stability of these high curvature assemblies. Molecular simulations here of polyethylene glycol (PEG) based systems show that a systematic increase in the hydrated PEG fraction, in both monodisperse and binary blends, induces budding and breakup into spherical and novel ‘dumbbell’ micelles—as seen in electron microscopy images of degradable worm-like micelles. Core dimension, d, in our large-scale, long-time dissipative particle dynamics (DPD) simulations is shown to scale with chain-length, N, as predicted theoretically by the strong segregation limit (d ≈ N2/3), but morphological transitions of binary mixtures are only crudely predicted by simple mixture rules. Here we show that for weakly demixing diblock copolymers, the coupling between local interfacial concentration and mean curvature can be described with a simple linear relationship. The computational methods developed here for PEG-based assemblies should be useful for many high curvature nanosystems

Force balance and membrane shedding at the Red Blood Cell surface

During the aging of the red-blood cell, or under conditions of extreme echinocytosis, membrane is shed from the cell plasma membrane in the form of nano-vesicles. We propose that this process is the result of the self-adaptation of the membrane surface area to the elastic stress imposed by the spectrin cytoskeleton, via the local buckling of membrane under increasing cytoskeleton stiffness. This model introduces the concept of force balance as a regulatory process at the cell membrane, and quantitatively reproduces the rate of area loss in aging red-blood cells.Comment: 4 pages, 3 figure

Residential green space and air pollution are associated with brain activation in a social-stress paradigm

We examined the influence of three major environmental variables at the place of residence as potential moderating variables for neurofunctional activation during a social-stress paradigm. Data from functional magnetic resonance imaging of 42 male participants were linked to publicly accessible governmental databases providing information on amount of green space, air pollution, and noise pollution. We hypothesized that stress-related brain activation in regions important for emotion regulation were associated positively with green space and associated negatively with air pollution and noise pollution. A higher percentage of green space was associated with stronger parietal and insular activation during stress compared with that in the control condition. More air pollution was associated with weaker activation in the same (but also extended) brain regions. These findings may serve as an important reference for future studies in the emerging field of “neuro-urbanism” and emphasize the importance of environmental factors in urban planning

Micro-Capsules in Shear Flow

This paper deals with flow-induced shape transitions of elastic capsules. The state of the art concerning both theory and experiments is briefly reviewed starting with dynamically induced small deformation of initially spherical capsules and the formation of wrinkles on polymerized membranes. Initially non-spherical capsules show tumbling and tank-treading motion in shear flow. Theoretical descriptions of the transition between these two types of motion assuming a fixed shape are at variance with the full capsule dynamics obtained numerically. To resolve the discrepancy, we expand the exact equations of motion for small deformations and find that shape changes play a dominant role. We classify the dynamical phase transitions and obtain numerical and analytical results for the phase boundaries as a function of viscosity contrast, shear and elongational flow rate. We conclude with perspectives on timedependent flow, on shear-induced unbinding from surfaces, on the role of thermal fluctuations, and on applying the concepts of stochastic thermodynamics to these systems.Comment: 34 pages, 15 figure

Field Theoretic Study of Bilayer Membrane Fusion: II. Mechanism of a Stalk-Hole Complex

We use self-consistent field theory to determine structural and energetic properties of intermediates and transition states involved in bilayer membrane fusion. In particular, we extend our original calculations from those of the standard hemifusion mechanism, which was studied in detail in the first paper of this series, to consider a possible alternative to it. This mechanism involves non-axial stalk expansion, in contrast to the axially symmetric evolution postulated in the classical mechanism. Elongation of the initial stalk facilitates the nucleation of holes and leads to destabilization of the fusing membranes via the formation of a stalk-hole complex. We study properties of this complex in detail, and show how transient leakage during fusion, previously predicted and recently observed in experiment, should vary with system architecture and tension. We also show that the barrier to fusion in the alternative mechanism is lower than that of the standard mechanism by a few $k_BT$ over most of the relevant region of system parameters, so that this alternative mechanism is a viable alternative to the standard pathway