Armin R. Volkel

Streptavidin tetramerization and 2D crystallization: a mean-field approach.

A mean-field theoretical approach is applied to streptavidin tetramerization and two-dimensional (2D) crystallization. This theory includes, in particular, solvent-residue interactions following the inhomogeneous Flory-Huggins model for polymers. It also takes into account residue-residue interactions by using tabulated pair interaction parameters. This theory allows one to explicitly calculate the entropy of the inhomogeneous system. We show that hydrophobic interactions are responsible for the stability of tetramerization. Within the present theory, the equilibrium distance between the two dimers is the same as that determined experimentally. The free energy of tetramerization (i.e., dissociation of the two dimers) is 50 k(B)T. Unlike tetramerization, hydrophobic interactions alone are not sufficient to stabilize the 2D crystal C(222), but solvent-mediated residue-residue interactions give the most important contribution.

A microarray MEMS device for biolistic delivery of vaccine and drug powders

We report a biolistic technology platform for physical delivery of particle formulations of drugs or vaccines using parallel arrays of microchannels, which generate highly collimated jets of particles with high spatial resolution. Our approach allows for effective delivery of therapeutics sequentially or concurrently (in mixture) at a specified target location or treatment area. We show this new platform enables the delivery of a broad range of particles with various densities and sizes into both in vitro and ex vivo skin models. Penetration depths of ∼1 mm have been achieved following a single ejection of 200 µg high-density gold particles, as well as 13.6 µg low-density polystyrene-based particles into gelatin-based skin simulants at 70 psi inlet gas pressure. Ejection of multiple shots at one treatment site enabled deeper penetration of ∼3 mm in vitro, and delivery of a higher dose of 1 mg gold particles at similar inlet gas pressure. We demonstrate that particle penetration depths can be optimized in vitro by adjusting the inlet pressure of the carrier gas, and dosing is controlled by drug reservoirs that hold precise quantities of the payload, which can be ejected continuously or in pulses. Future investigations include comparison between continuous versus pulsatile payload deliveries. We have successfully delivered plasmid DNA (pDNA)-coated gold particles (1.15 µm diameter) into ex vivo murine and porcine skin at low inlet pressures of ∼30 psi. Integrity analysis of these pDNA-coated gold particles confirmed the preservation of full-length pDNA after each particle preparation and jetting procedures. This technology platform provides distinct capabilities to effectively deliver a broad range of particle formulations into skin with specially designed high-speed microarray ejector nozzles.

Meanfield approach to the thermodynamics of protein-solvent systems with application to p53.

We present a meanfield theoretical approach for studying protein-solvent interactions. Starting with the partition function of the system, we develop a field theory by introducing densities for the different components of the system. At this point, protein-solvent interactions are introduced following the inhomogeneous Flory-Huggins model for polymers. Finally, we calculate the free energy in a meanfield approximation. We apply this method to study the stability of the tetramerization domain of the tumor suppressor protein p53 when subjected to site-directed mutagenesis. The four chains of this protein are held together by hydrophobic interactions, and some mutations can weaken this bond while preserving the secondary structure of the single protein chains. We find good qualitative agreement between our numerical results and experimental data, thus encouraging the use of this method as a guide in designing experiments.

Structural stability of oligomeric proteins: A mean-field theoretical approach

We present a mean-field approach for calculating thermodynamic properties(free energies) of protein–solvent systems. We apply this method to thetumor suppressor protein p53, where we study the stability of itstetramerization domain when subjected to site-directed mutagenesis. Acomparison with experimental results is included.

Mean-field approach to the thermodynamics of complex solids

SummaryWe propose a mean-field approach for calculating the thermodynamic properties of complex solids. We illustrate this method by applying it to a simple mono-atomic solid. A comparison with solid Argon allows us to evaluate the method for accuracy and computational efficiency. Applications to more complex materials such as macromolecular systems are discussed.