Micellization in the presence of polyelectrolyte

We present a simple model to study micellization of amphiphiles condensed on a rodlike polyion. Although the mean field theory leads to a first order micellization transition for sufficiently strong hydrophobic interactions, the simulations show that no such thermodynamic phase transition exists. Instead, the correlations between the condensed amphiphiles can result in a structure formation very similar to micelles.Comment: 8 pages, 7 figure

Electrostatic colloid-membrane complexation

We investigate numerically and on the scaling level the adsorption of a charged colloid on an oppositely charged flexible membrane. We show that the long ranged character of the electrostatic interaction leads to a wrapping reentrance of the complex as the salt concentration is varied. The membrane wrapping depends on the size of the colloid and on the salt concentration and only for intermediate salt concentration and colloid sizes we find full wrapping. From the scaling model we derive simple relations for the phase boundaries between the different states of the complex, which agree well with the numerical minimization of the free energy.Comment: 7 page, 11 figure

Safety and Short-Term Toxicity of a Novel Cationic Lipid Formulation for Human Gene Therapy

Overview summary Although several viral vectors have been widely applied to the treatment of human disease, the development of nonviral vectors is still in their infancy. In this report, a novel cationic lipid, DMRIE/DOPE, has been incorporated into the DNA–liposome formulation that improves transfection efficiencies and allows up to 1,000-fold higher concentrations of DNA to be administered in vivo. In this paper, the safety and toxicity of this formulation is described in two species, mice and pigs, suggesting that it may prove useful for human gene therapy.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/63224/1/hum.1993.4.6-781.pd

Sliding Columnar Phase of DNA-Lipid Complexes

We introduce a simple model for DNA-cationic-lipid complexes in which galleries between planar bilayer lipid lamellae contain DNA 2D smectic lattices that couple orientationally and positionally to lattices in neighboring galleries. We identify a new equilibrium phase in which there are long-range orientational but not positional correlations between DNA lattices. We discuss properties of this new phase such as its X-ray structure factor S(r), which exhibits unusual exp(- const.ln^2 r) behavior as a function of in-plane separation r.Comment: This file contains 4 pages of double column text and one postscript figure. This version includes interactions between dislocations in a given gallery and presents an improved estimate of the decoupling temperature. It is the published versio

Nonlinear Elasticity of the Sliding Columnar Phase

The sliding columnar phase is a new liquid-crystalline phase of matter composed of two-dimensional smectic lattices stacked one on top of the other. This phase is characterized by strong orientational but weak positional correlations between lattices in neighboring layers and a vanishing shear modulus for sliding lattices relative to each other. A simplified elasticity theory of the phase only allows intralayer fluctuations of the columns and has three important elastic constants: the compression, rotation, and bending moduli, $B$, $K_y$, and $K$. The rotationally invariant theory contains anharmonic terms that lead to long wavelength renormalizations of the elastic constants similar to the Grinstein-Pelcovits renormalization of the elastic constants in smectic liquid crystals. We calculate these renormalizations at the critical dimension $d=3$ and find that $K_y(q) \sim K^{1/2}(q) \sim B^{-1/3}(q) \sim (\ln(1/q))^{1/4}$, where $q$ is a wavenumber. The behavior of $B$, $K_y$, and $K$ in a model that includes fluctuations perpendicular to the layers is identical to that of the simple model with rigid layers. We use dimensional regularization rather than a hard-cutoff renormalization scheme because ambiguities arise in the one-loop integrals with a finite cutoff.Comment: This file contains 18 pages of double column text in REVTEX format and 6 postscript figure

A New Cationic Liposome DNA Complex Enhances the Efficiency of Arterial Gene Transfer In Vivo

Overview summary GAP-DLRIE/DOPE, a new cationic liposome preparation, is an efficient liposomal vector that increases gene expression in arteries compared to naked DNA or previously described cationic DNA–liposome complexes by more than 15-fold. Although less efficient than adenoviral gene transfer, these levels of gene expression represent a significant improvement in liposome transfection in vivo and approach levels observed with clinically acceptable doses of adenoviral vectors. The improvement in gene expression, together with the relative safety associated with liposomal gene transfer, suggests that such nonviral vectors may be appropriate for human gene therapy protocols which utilize catheter-based gene delivery.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/63105/1/hum.1996.7.15-1803.pd

Biosignatures of Exposure/Transmission and Immunity.

A blood test that captures cumulative exposure over time and assesses levels of naturally acquired immunity (NAI) would provide a critical tool to monitor the impact of interventions to reduce malaria transmission and broaden our understanding of how NAI develops around the world as a function of age and exposure. This article describes a collaborative effort in multiple International Centers of Excellence in Malaria Research (ICEMRs) to develop such tests using malaria-specific antibody responses as biosignatures of transmission and immunity. The focus is on the use of Plasmodium falciparum and Plasmodium vivax protein microarrays to identify a panel of the most informative antibody responses in diverse malaria-endemic settings representing an unparalleled spectrum of malaria transmission and malaria species mixes before and after interventions to reduce malaria transmission

The Influence of B Cell Depletion Therapy on Naturally Acquired Immunity to Streptococcus pneumoniae

The anti-CD20 antibody Rituximab to deplete CD20+ B cells is an effective treatment for rheumatoid arthritis and B cell malignancies, but is associated with an increased incidence of respiratory infections. Using mouse models we have investigated the consequences of B cell depletion on natural and acquired humoral immunity to Streptococcus pneumoniae. B cell depletion of naïve C57Bl/6 mice reduced natural IgM recognition of S. pneumoniae, but did not increase susceptibility to S. pneumoniae pneumonia. ELISA and flow cytometry assays demonstrated significantly reduced IgG and IgM recognition of S. pneumoniae in sera from mice treated with B cell depletion prior to S. pneumoniae nasopharyngeal colonization compared to untreated mice. Colonization induced antibody responses to protein rather than capsular antigen, and when measured using a protein array B cell depletion prior to colonization reduced serum levels of IgG to several protein antigens. However, B cell depleted S. pneumoniae colonized mice were still partially protected against both lung infection and septicemia when challenged with S. pneumoniae after reconstitution of their B cells. These data indicate that although B cell depletion markedly impairs antibody recognition of S. pneumoniae in colonized mice, some protective immunity is maintained, perhaps mediated by cellular immunity

Atomistic Modeling of F-Actin Mechanical Responses and Determination of Mechanical Properties

A molecular structural mechanics (MSM) model was developed for F-actins in cells, where the force constants describing the monomer interaction were achieved using molecular dynamics simulations. The MSM was then employed to predict the mechanical properties of F-actin. The obtained Young’s modulus (1.92 GPa), torsional rigidity (2.36 × 10–26 Nm2), and flexural rigidity (10.84 × 10–26 Nm2) were found to be in good agreement with existing experimental data. Subsequently, the tension-induced bending was studied for F-actins as a result of their helical structure. Mechanical instability was also investigated for the actin filaments in filopodial protrusion by considering the reinforcing effect of the actin-binding proteins. The predicted buckling load agreed well with the experimentally obtained stall force, showing a pivotal role of the actin-binding protein in regulating the stiffness of F-actin bundles during the formation of filopodia protrusion. Herein, it is expected that the MSM model can be extended to the mechanics of more complex filamentous systems such as stress fibers and actin meshwork