173 research outputs found
A surface forces platform for dielectric measurements
Methods are described to implement dielectric spectroscopy (frequency range 10(-1)-10(6) Hz) within a surface forces apparatus by using as electrodes silver sheets on the backside of mica. These methods are applied to study the competitive effects of surface alignment, confinement, and shear field on 5CB (5-cyanobiphenyl), a nematic liquid crystal at the experimental temperature of 25degreesC. In the planar orientation, films could be squeezed to a minimum thickness of approximate to5 Angstrom, the molecule's thickness. In the perpendicular (homeotropic) orientation, films could be squeezed to approximate to25 Angstrom, the expected thickness of the head-to-tail 5CB dimer. It was difficult to discuss responses at f >10(5) Hz quantitatively because the peak was not visible in the experimental frequency window. Nonetheless, the onset of the relaxation mode for the planar oriented molecules appears at higher frequency than for the homeotropic orientation. A slower relaxation mode, peaked at f approximate to 10 Hz, was assigned to electrode polarization due to the mobility of trace ions within the 5CB samples although these samples were >99.7% pure. The peak frequency was a factor of 3 slower with homeotropic than planar alignment and, in both cases, independent of film thickness except when the film thickness exceeded 10 mum. This was explained using a simple model based on the assumption that trace ions move to oppositely charged electrodes to form electric double layers. A small influence of shear on the dielectric response was observed but only when the dielectric response was measured at the same frequency as the large-amplitude shear deformation. Also described is the use of capacitance to measure force-distance profiles.open8
Sliding Phases in XY-Models, Crystals, and Cationic Lipid-DNA Complexes
We predict the existence of a totally new class of phases in weakly coupled,
three-dimensional stacks of two-dimensional (2D) XY-models. These ``sliding
phases'' behave essentially like decoupled, independent 2D XY-models with
precisely zero free energy cost associated with rotating spins in one layer
relative to those in neighboring layers. As a result, the two-point spin
correlation function decays algebraically with in-plane separation. Our
results, which contradict past studies because we include higher-gradient
couplings between layers, also apply to crystals and may explain recently
observed behavior in cationic lipid-DNA complexes.Comment: 4 pages of double column text in REVTEX format and 1 postscript
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Elastic deformation of a fluid membrane upon colloid binding
When a colloidal particle adheres to a fluid membrane, it induces elastic
deformations in the membrane which oppose its own binding. The structural and
energetic aspects of this balance are theoretically studied within the
framework of a Helfrich Hamiltonian. Based on the full nonlinear shape
equations for the membrane profile, a line of continuous binding transitions
and a second line of discontinuous envelopment transitions are found, which
meet at an unusual triple point. The regime of low tension is studied
analytically using a small gradient expansion, while in the limit of large
tension scaling arguments are derived which quantify the asymptotic behavior of
phase boundary, degree of wrapping, and energy barrier. The maturation of
animal viruses by budding is discussed as a biological example of such
colloid-membrane interaction events.Comment: 14 pages, 9 figures, REVTeX style, follow-up on cond-mat/021242
Structural Properties of the Sliding Columnar Phase in Layered Liquid Crystalline Systems
Under appropriate conditions, mixtures of cationic and neutral lipids and DNA
in water condense into complexes in which DNA strands form local 2D smectic
lattices intercalated between lipid bilayer membranes in a lamellar stack.
These lamellar DNA-cationic-lipid complexes can in principle exhibit a variety
of equilibrium phases, including a columnar phase in which parallel DNA strands
from a 2D lattice, a nematic lamellar phase in which DNA strands align along a
common direction but exhibit no long-range positional order, and a possible new
intermediate phase, the sliding columnar (SC) phase, characterized by a
vanishing shear modulus for relative displacement of DNA lattices but a
nonvanishing modulus for compressing these lattices. We develop a model capable
of describing all phases and transitions among them and use it to calculate
structural properties of the sliding columnar phase. We calculate displacement
and density correlation functions and x-ray scattering intensities in this
phase and show, in particular, that density correlations within a layer have an
unusual dependence on separation r. We
investigate the stability of the SC phase with respect to shear couplings
leading to the columnar phase and dislocation unbinding leading to the lamellar
nematic phase. For models with interactions only between nearest neighbor
planes, we conclude that the SC phase is not thermodynamically stable.
Correlation functions in the nematic lamellar phase, however, exhibit SC
behavior over a range of length scalesComment: 28 pages, 4 figure
Dynamic phase separation of fluid membranes with rigid inclusions
Membrane shape fluctuations induce attractive interactions between rigid
inclusions. Previous analytical studies showed that the fluctuation-induced
pair interactions are rather small compared to thermal energies, but also that
multi-body interactions cannot be neglected. In this article, it is shown
numerically that shape fluctuations indeed lead to the dynamic separation of
the membrane into phases with different inclusion concentrations. The tendency
of lateral phase separation strongly increases with the inclusion size. Large
inclusions aggregate at very small inclusion concentrations and for relatively
small values of the inclusions' elastic modulus.Comment: 6 pages, 6 figure
Therapeutic efficacy in a hemophilia B model using a biosynthetic mRNA liver depot system
DNA-based gene therapy has considerable therapeutic potential, but the challenges associated with delivery continue to limit progress. Messenger RNA (mRNA) has the potential to provide for transient production of therapeutic proteins, without the need for nuclear delivery and without the risk of insertional mutagenesis. Here we describe the sustained delivery of therapeutic proteins in vivo in both rodents and non-human primates via nanoparticle-formulated mRNA. Nanoparticles formulated with lipids and lipid-like materials were developed for delivery of two separate mRNA transcripts encoding either human erythropoietin (hEPO) or factor IX (hFIX) protein. Dose-dependent protein production was observed for each mRNA construct. Upon delivery of hEPO mRNA in mice, serum EPO protein levels reached several orders of magnitude (>125 000-fold) over normal physiological values. Further, an increase in hematocrit (Hct) was established, demonstrating that the exogenous mRNA-derived protein maintained normal activity. The capacity of producing EPO in non-human primates via delivery of formulated mRNA was also demonstrated as elevated EPO protein levels were observed over a 72-h time course. Exemplifying the possible broad utility of mRNA drugs, therapeutically relevant amounts of human FIX (hFIX) protein were achieved upon a single intravenous dose of hFIX mRNA-loaded lipid nanoparticles in mice. In addition, therapeutic value was established within a hemophilia B (FIX knockout (KO)) mouse model by demonstrating a marked reduction in Hct loss following injury (incision) to FIX KO mice
The multiple faces of self-assembled lipidic systems
Lipids, the building blocks of cells, common to every living organisms, have the propensity to self-assemble into well-defined structures over short and long-range spatial scales. The driving forces have their roots mainly in the hydrophobic effect and electrostatic interactions. Membranes in lamellar phase are ubiquitous in cellular compartments and can phase-separate upon mixing lipids in different liquid-crystalline states. Hexagonal phases and especially cubic phases can be synthesized and observed in vivo as well. Membrane often closes up into a vesicle whose shape is determined by the interplay of curvature, area difference elasticity and line tension energies, and can adopt the form of a sphere, a tube, a prolate, a starfish and many more. Complexes made of lipids and polyelectrolytes or inorganic materials exhibit a rich diversity of structural morphologies due to additional interactions which become increasingly hard to track without the aid of suitable computer models. From the plasma membrane of archaebacteria to gene delivery, self-assembled lipidic systems have left their mark in cell biology and nanobiotechnology; however, the underlying physics is yet to be fully unraveled
Membrane-mediated interactions
Interactions mediated by the cell membrane between inclusions, such as
membrane proteins or antimicrobial peptides, play important roles in their
biological activity. They also constitute a fascinating challenge for
physicists, since they test the boundaries of our understanding of
self-assembled lipid membranes, which are remarkable examples of
two-dimensional complex fluids. Inclusions can couple to various degrees of
freedom of the membrane, resulting in different types of interactions. In this
chapter, we review the membrane-mediated interactions that arise from direct
constraints imposed by inclusions on the shape of the membrane. These effects
are generic and do not depend on specific chemical interactions. Hence, they
can be studied using coarse-grained soft matter descriptions. We deal with
long-range membrane-mediated interactions due to the constraints imposed by
inclusions on membrane curvature and on its fluctuations. We also discuss the
shorter-range interactions that arise from the constraints on membrane
thickness imposed by inclusions presenting a hydrophobic mismatch with the
membrane.Comment: 38 pages, 10 figures, pre-submission version. In: Bassereau P., Sens
P. (eds) Physics of Biological Membranes. Springer, Cha
Rule-Based Cell Systems Model of Aging using Feedback Loop Motifs Mediated by Stress Responses
Investigating the complex systems dynamics of the aging process requires integration of a broad range of cellular processes describing damage and functional decline co-existing with adaptive and protective regulatory mechanisms. We evolve an integrated generic cell network to represent the connectivity of key cellular mechanisms structured into positive and negative feedback loop motifs centrally important for aging. The conceptual network is casted into a fuzzy-logic, hybrid-intelligent framework based on interaction rules assembled from a priori knowledge. Based upon a classical homeostatic representation of cellular energy metabolism, we first demonstrate how positive-feedback loops accelerate damage and decline consistent with a vicious cycle. This model is iteratively extended towards an adaptive response model by incorporating protective negative-feedback loop circuits. Time-lapse simulations of the adaptive response model uncover how transcriptional and translational changes, mediated by stress sensors NF-κB and mTOR, counteract accumulating damage and dysfunction by modulating mitochondrial respiration, metabolic fluxes, biosynthesis, and autophagy, crucial for cellular survival. The model allows consideration of lifespan optimization scenarios with respect to fitness criteria using a sensitivity analysis. Our work establishes a novel extendable and scalable computational approach capable to connect tractable molecular mechanisms with cellular network dynamics underlying the emerging aging phenotype
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