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Biomedical subjects

Zlatko Vasilkoski

Publications and source records attributed to Zlatko Vasilkoski.

3 recordsLinked to original sources

Membrane electroporation: The absolute rate equation and nanosecond time scale pore creation.

The recent applications of nanosecond, megavolt-per-meter electric field pulses to biological systems show striking cellular and subcellular electric field induced effects and revive the interest in the biophysical mechanism of electroporation. We first show that the absolute rate theory, with experimentally based parameter input, is consistent with membrane pore creation on a nanosecond time scale. Secondly we use a Smoluchowski equation-based model to formulate a self-consistent theoretical approach. The analysis is carried out for a planar cell membrane patch exposed to a 10 ns trapezoidal pulse with 1.5 ns rise and fall times. Results demonstrate reversible supraelectroporation behavior in terms of transmembrane voltage, pore density, membrane conductance, fractional aqueous area, pore distribution, and average pore radius. We further motivate and justify the use of Krassowska's asymptotic electroporation model for analyzing nanosecond pulses, showing that pore creation dominates the electrical response and that pore expansion is a negligible effect on this time scale.

Cell Membrane↗

Microdosimetry for conventional and supra-electroporation in cells with organelles.

Conventional electroporation (EP) by 0.1 to 1 kV/cm pulses longer than 100 micros, and supra-electroporation by 10 to 300 kV/cm pulses shorter than 1 micros cause different cellular effects. Conventional EP delivers DNA, proteins, small drugs, and fluorescent indicators across the plasma membrane (PM) and causes moderate levels of phosphatidylserine (PS) translocation at the PM. We hypothesize that supra-EP is central to intracellular effects such as apoptosis induction and higher levels of PS translocation. Our cell system model has 20,000 interconnected local models for small areas of the PM and organelle membranes, small regions of aqueous media, appropriate resting potentials, and the asymptotic EP model. Conventional EP primarily affects the PM, but with a hint of endoplasmic reticulum involvement. Supra-EP can involve all of a cell's membrane at the largest fields. Conventional EP fields tend to go around cells, but supra-EP fields go through cells, extensively penetrating organelles.

Cell Physiological Phenomena↗

Diffusion-collision model algorithms for protein folding kinetics.

The diffusion-collision model (DCM) of protein folding is described qualitatively and quantitatively. The input parameters required to perform a calculation are explained, and the output data are outlined. Three examples are given of calculating DCM folding kinetics: the Engrailed Homeodomain (a three-helix bundle with three helical microdomains, pdb code 1ENH), protein G (with three microdomains having a beta-hairpin-alpha-helix-beta-hairpin motif, pdb code 1PGA), and apomyoglobin (with eight helices and seven strong microdomain-microdomain pairings).

Algorithms↗