Transport on a Lattice with Dynamical Defects

Many transport processes in nature take place on substrates, often considered as unidimensional lanes. These unidimensional substrates are typically non-static: affected by a fluctuating environment, they can undergo conformational changes. This is particularly true in biological cells, where the state of the substrate is often coupled to the active motion of macromolecular complexes, such as motor proteins on microtubules or ribosomes on mRNAs, causing new interesting phenomena. Inspired by biological processes such as protein synthesis by ribosomes and motor protein transport, we introduce the concept of localized dynamical sites coupled to a driven lattice gas dynamics. We investigate the phenomenology of transport in the presence of dynamical defects and find a novel regime characterized by an intermittent current and subject to severe finite-size effects. Our results demonstrate the impact of the regulatory role of the dynamical defects in transport, not only in biology but also in more general contexts

Investigation of qq-dependent dynamical heterogeneity in a colloidal gel by x-ray photon correlation spectroscopy

We use time-resolved X-Photon Correlation Spectroscopy to investigate the slow dynamics of colloidal gels made of moderately attractive carbon black particles. We show that the slow dynamics is temporally heterogeneous and quantify its fluctuations by measuring the variance $\chi$ of the instantaneous intensity correlation function. The amplitude of dynamical fluctuations has a non-monotonic dependence on scattering vector $q$, in stark contrast with recent experiments on strongly attractive colloidal gels [Duri and Cipelletti, \textit{Europhys. Lett.} \textbf{76}, 972 (2006)]. We propose a simple scaling argument for the $q$-dependence of fluctuations in glassy systems that rationalizes these findings.Comment: Final version published in PR

Tumor transfection after systemic injection of DNA lipid nanocapsules

With the goal of generating an efficient vector for systemic gene delivery, a new kind of nanocarrier consisting of lipid nanocapsules encapsulating DOTAP/DOPE lipoplexes (DNA LNCs) was pegylated by the post-insertion of amphiphilic and flexible polymers. The aim of this surface modification was to create a long-circulating vector, able to circulate in the blood stream and efficient in transfecting tumoral cells after passive targeting by enhanced permeability and retention effect (EPR effect). PEG conformation, electrostatic features, and hydrophylicity are known to be important factors able to influence the pharmacokinetic behaviour of vectors. In this context, the surface structure characteristics of the newly pegylated DNA LNCs were studied by measuring electrophoretic mobility as a function of ionic strength in order to establish a correlation between surface properties and in vivo performance of the vector. Finally, thanks to this PEGylation, gene expression was measured up to 84-fold higher in tumor compared to other tested organs after intravenous injection. The present results indicate that PEGylated DNA LNCs are promising carriers for an efficient cancer gene therapy

The encapsulation of DNA molecules within biomimetic lipid nanocapsules

Most of DNA synthetic complexes result from the self-assembly of DNA molecules with cationic lipids or polymers in an aqueous controlled medium. However, injection of such self-assembled complexes in medium like blood that differ from that of their formulation leads to strong instability. Therefore, DNA vectors that have physico-chemical properties and structural organisation that will not be sensitive to a completely different medium in terms of ionic and protein composition are actively sought. To this end, the goal here was to discover and optimize a nanostructured system where DNA molecules would be encapsulated in nanocapsules consisting in an oily core and a shell covered by PEG stretches obtained through a nanoemulsion process in the absence of organic solvent. This encapsulation form of DNA molecules would prevent interactions with external hostile biological fluid. The results show the entrapment of lipoplexes into lipid nanocapsules, leading to the formation of neutral 110 nm-DNA nanocapsules. They were weakly removed by the immune system, displaying an increased blood half-life, and improved carcinoma cell transfection, in comparison to the parent lipoplexes. Our results demonstrate that the fabrication of nanocapsules encapsulating hydrophilic DNA in an oily core that meet criteria for blood injection is possible

Non-viral nanosystems for systemic siRNA delivery

To use siRNA (small interfering ribonucleic acids) for systemic administration, a delivery system is often necessary to overcome barriers between administration and the target sites. These delivery systems require different properties to be efficient. On the one hand, they have to protect siRNA from degradation and/or inactivation and, on the other hand, they have themselves to be stable in blood and possess stealth properties to avoid elimination and degradation. Active and/or passive targeting should help the delivery system to reach the desired cell type or tissue, to be internalised, and to deliver siRNA to the cytoplasm so that siRNA can act by RNA interference and inhibit protein synthesis. This review presents an overview of different non-viral delivery systems, which have been evaluated in vivo or entered in clinical trials, with a focus on their physicochemical properties in order to help the development of new and efficient siRNA delivery systems, as the therapeutic solutions of tomorrow

Formulation of nanocarriers for systemic delivery of nucleic acids

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Folding and unfolding kinetics of a single semiflexible polymer

We theoretically investigate the kinetics of the folding transition of a single semiflexible polymer. In the folding transition, the growth rate decrease with an increase in the number of monomers in a collapsed domain, suggesting that the main contribution to dissipation is from the motion of the domain. In the unfolding transition, dynamic scaling exponents, 1/8 and 1/4, were determined for disentanglement and relaxation steps, respectively. We performed Langevin dynamics simulations to test our theory. It is found that our theory is in good agreement with simulations. We also propose the kinetics of the transitions in the presence of the hydrodynamic interaction.Comment: 12 pages, 10 figure

Injected Power Fluctuations in 1D Dissipative Systems

Using fermionic techniques, we compute exactly the large deviation function (ldf) of the time-integrated injected power in several one-dimensional dissipative systems of classical spins. The dynamics are T=0 Glauber dynamics supplemented by an injection mechanism, which is taken as a Poissonian flipping of one particular spin. We discuss the physical content of the results, specifically the influence of the rate of the Poisson process on the properties of the ldf.Comment: 18 pages, 8 figure

Formulation and characterization of suRNA LNC

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