Gene delivery and immunomodulatory effects of plasmid DNA associated with Branched Amphiphilic Peptide Capsules.

We recently reported on a new class of branched amphiphilic peptides that associate with double stranded DNA and promote in vitro transfection of eukaryotic cells. In the present study, we tested a different formulation in which plasmid DNA associates with the surface of preformed 20-30nm cationic capsules formed through the self-assembly of the two branched amphiphilic peptides. Under these conditions, the negatively charged DNA interacts with the cationic surface of the Branched Amphiphilic Peptide Capsules (BAPCs) through numerous electrostatic interactions generating peptide-DNA complexes with sizes ranging from 50 to 250nm. The BAPCs-DNA nanoparticles are capable of delivering plasmid DNA of different size into cells in culture, yielding high transfection rates and minimal cytotoxicity. Furthermore, BAPCs were tested for in vivo delivery of a DNA vaccine previously designed to activate immune responses and capable of controlling tumors induced by type 16 human papilloma virus (HPV-16). The BAPCs-DNA nanoparticles enhanced the vaccine-induced antitumor protection and promoted activation of murine dendritic cells without significant toxic effects. These results indicate that branched amphiphilic oligo-peptides nanoparticles represent a new and promising nonviral DNA/gene delivery approach endowing immunomodulatory properties for DNA vaccines.

Comment on "Print your atomic force microscope" [Rev. Sci. Instrum. 78, 075105 (2007)].

The paper of Kühner et al. [Rev. Sci. Instrum. 78, 075105 (2007)], presents a sound realization of a very nice idea. Namely, to design and prepare (via rapid prototyping) a custom head for atomic force microscope (AFM). Custom AFM heads are essential for various applications, which include the AFM force spectroscopy modes and convenient AFM coupling with other techniques. Our comment concerns the deflection data for a thermally driven AFM cantilever obtained by Kühner et al. using their AFM setup (Figure 3 therein). The results of Kühner et al. imply that a thermally excited AFM cantilever vibrates with aberrantly large amplitudes. Namely, the deflection noise amplitudes for the MLCT-D cantilever are 60-100 times larger than what is typically observed in our lab and by others. As we argue, the author's mistake is likely attributed to an improper usage of the AFM bandwidth. We explain the necessary correction and discuss the issue of bandwidth for the AFM force spectroscopy measurements.

Quantitative measure of nanoscale adhesion hysteresis by ultrasonic force microscopy.

Adhesion hysteresis is the difference between the work used on separating two surfaces and the work gained on bringing them back together. Although much effort has been invested into adhesion hysteresis investigations at macroscales and microscales, its measurements at the nanolengths or even molecular lengths are still not easy. In this paper we demonstrate how to obtain quantitative measures of local adhesion hysteresis from ultrasonic force microscopy investigations. We derive analytical models fitting all the experimental cases and apply them to experimental data.

Correlations between adhesion hysteresis and friction at molecular scales.

Correlations between adhesion hysteresis and local friction are theoretically and experimentally investigated. The model is based on the classical theory of adhesional friction, contact mechanics, capillary hysteresis, and nanoscale roughness. Adhesion hysteresis was found to scale with friction through the scaling factor containing a varying ratio of adhesion energy over the reduced Young's modulus. Capillary forces can offset the relationship between adhesion hysteresis and friction. Measurements on a wide range of engineering samples with varying adhesive and elastic properties confirm the model. Adhesion hysteresis is investigated under controlled, low humidity atmosphere via ultrasonic force microscopy. Friction is measured by the friction force microscopy.