Biophysical aspects of dielectrophoresis

Dielectrophoresis, the translational motion produced by the action of a nonuniform electric field upon neutral polarizable bodies, is proving useful in handling biological systems. It is especially useful in studies of suspensions of cells. Normal and abnormal cells respond differently, and may be separated on the basis of their differing polarizational response. Because the phenomenon depends upon the polarization and not upon the charge of the particles, subtle new differences are available for exploitation by dielectrophoresis. Operation can be carried out in a high frequency electric field. The frequency spectrum of cellular response to dielectrophoresis varies with the species, and with the physiological state of the individual cell. Cells may be studied individually or in large numbers at a time. Cells may be gathered and formed into fleshlike aggregates using dielectrophoresis.Extension of the techniques to the study of the fundamental nature of the polarizabilities of cells and subcellular particles should provide useful insight into the roles of electronic, atomic dipole orientational, and nomadic polarization, as well as that due to interfacial (Maxwell-Wagner) polarization in biological systems.     

Biophysical aspects of cancer--electromagnetic mechanism

Hypothesis of coherent vibration states in biological systems based on nonlinear interaction between longitudinal elastic and electric polarization fields with metabolic energy supply was formulated by Frohlich. Conditions for excitation of coherent states and generation of electromagnetic fields are satisfied in microtubules which form electrical polar structures. Numerical models are used for analysis of Frohlich's vibration states in cells. Reduction of activity and of energy production in mitochondria, and disintegration of cytoskeleton structures by phosphorylation on the pathway of cancer trasformation can diminish excitation of the Frohlich's vibration states and of the generated electromagnetic field, which results in disturbances of the interaction forces between cells. Interaction forces between cancer cells may be smaller than interaction forces between healthy cells and cancer cells as follows from numerical models. Mechanism of malignity, i.e. local invasion, detachment of cancer cells, and metastasis, is assumed to depend on the electromagnetic field.     

Biophysical aspects of intra-protein proton transfer

The passage of proton trough proteins is common to all membranal energy conserving enzymes. While the routes differ among the various proteins, the mechanism of proton propagation is based on the same chemical-physical principles. The proton progresses through a sequence of dissociation association steps where the protein and water molecules function as a solvent that lowers the energy penalty associated with the generation of ions in the protein. The propagation of the proton in the protein is a random walk, between the temporary proton binding sites that make the conducting path, that is biased by the intra-protein electrostatic potential. Kinetic measurements of proton transfer reactions, in the sub-ns up to micros time frame, allow to monitor the dynamics of the partial reactions of an overall proton transfer through a protein.     

Biophysical chemical aspects of cellular cryobehavior

Freezing tolerance and resistance in nature are among the most important and challenging aspects of biochemical adaptation to extreme environments. Some biochemical strategies are known but their mechanism is still poorly understood. Cryopreservation of cells and tissues of sensitive organisms is still generally based on physical chemistry rather than on biophysical chemical mechanisms. This paper describes the main aspects of these problems and features new trends in their study.     

Zinc essentiality and toxicity. Biophysical aspects

The current concepts concerning zinc biology, its metabolism and transport into cells, its homeostasis, its role in the functioning of the human immune and endocrine systems, its participation in cell signaling, and its cytotoxicity, as well as the biophysical mechanisms of action of zinc ions at elevated concentrations on human blood cells are reviewed and analyzed.     

Biophysical aspects of using liposomes as delivery vehicles

Liposomes are used as biocompatible carriers of drugs, peptides, proteins, plasmic DNA, antisense oligonucleotides or ribozymes, for pharmaceutical, cosmetic, and biochemical purposes. The enormous versatility in particle size and in the physical parameters of the lipids affords an attractive potential for constructing tailor-made vehicles for a wide range of applications. Some of the recent literature will be reviewed here and presented from a biophysical point of view, thus providing a background for the more specialized articles in this special issue on liposome technology. Different properties (size, colloidal behavior, phase transitions, and polymorphism) of diverse lipid formulations (liposomes, lipoplexes, cubic phases, emulsions, and solid lipid nanoparticles) for distinct applications (parenteral, transdermal, pulmonary, and oral administration) will be rationalized in terms of common structural, thermodynamic and kinetic parameters of the lipids. This general biophysical basis helps to understand pharmaceutically relevant aspects such as liposome stability during storage and towards serum, the biodistribution and specific targeting of cargo, and how to trigger drug release and membrane fusion. Methods for the preparation and characterization of liposomal formulations in vitro will be outlined, too.     

Biophysical aspects of microsphere engulfment by human neutrophils.

A quantitative investigation into the mechanism of neutrophil phagocytosis of opsonized microspheres possessing well defined dimensions was undertaken. Three aspects were documented: membrane conservation, cell adhesion to the spheres, and active cell cytoplasmic projection around the microspheres. The physical act of internalizing a particle by a cell involves a reduction in its plasma membrane area and an increase in its volume. As a consequence, a cell can internalize only a finite number of particles. A store of membrane area exists on cytoplasmic granules and may be recruited during phagocytosis. Previous measurements of neutrophil membrane area and volume served as a basis for estimates of the maximum number of internalized microspheres. A comparison with experimental prediction based on membrane conservation and degranulation agrees within 10% for a range of microsphere diameters, from 0.5 to 8 microns. This suggests that the limitation for additional particle uptake in the population of engorged neutrophils is the lack of excess plasma membrane area. In a random population of neutrophils, there was a sub-group, approximately 40%, which could no longer phagocytose before depleting their membrane stores. Several aspects of the engulfment process were investigated to elucidate the cause of this phagocytosis deficiency. It could be shown by single cell observation that these cases were associated with a lack of pseudopod projection, although adhesion was still evident between the cell membrane and the microspheres.     

Biophysical aspects of neutron scattering from vibrational modes of proteins

This review describes a major portion of the published work on neutron scattering experiments aimed at measuring large scale motions in proteins. The importance of these motions for enzyme function and oxygen transport is indicated. The theory applicable to each type of neutron scattering measurement is given and results are discussed with a view to biological relevance. New experiments are suggested and a comparison of neutron scattering data is made with results from other techniques such as raman scattering, infrared absorption, photolysis and molecular dynamics simulations.     

Biophysical aspects of resource acquisition and competition in algal mixotrophs

Mixotrophic organisms combine autotrophic and heterotrophic nutrition and are abundant in both freshwater and marine environments. Recent observations indicate that mixotrophs constitute a large fraction of the biomass, bacterivory, and primary production in oligotrophic environments. While mixotrophy allows greater flexibility in terms of resource acquisition, any advantage must be traded off against an associated increase in metabolic costs, which appear to make mixotrophs uncompetitive relative to obligate autotrophs and heterotrophs. Using an idealized model of cell physiology and community competition, we identify one mechanism by which mixotrophs can effectively outcompete specialists for nutrient elements. At low resource concentrations, when the uptake of nutrients is limited by diffusion toward the cell, the investment in cell membrane transporters can be minimized. In this situation, mixotrophs can acquire limiting elements in both organic and inorganic forms, outcompeting their specialist competitors that can utilize only one of these forms. This advantage can be enough to offset as much as a twofold increase in additional metabolic costs incurred by mixotrophs. This mechanism is particularly relevant for the maintenance of mixotrophic populations and productivity in the highly oligotrophic subtropical oceans.     

Biophysical aspects and biological implications of the interaction of benzophenanthridine alkaloids with DNA

Benzophenanthridine alkaloids represent a very interesting and significant group of natural products that exhibit a broad range of biological and pharmacological properties. Among this group of alkaloids, sanguinarine, nitidine, fagaronine, and chelerythrine have the potential to form molecular complexes with DNA structures and have attracted recent attention for their possible clinical and pharmacological utility. This review focuses on the interaction of these alkaloids with polymorphic DNA structures (B-form, Z-form, H^L-form, and triple helical form) reported by several research groups employing various physical techniques such as spectrophotometry, spectrofluorimetry, circular dichroism, NMR spectroscopy, thermal melting, viscometry as well as thermodynamic analysis by isothermal titration calorimetry and differential scanning calorimetry to elucidate the mode and mechanism of action at the molecular level to determine the structure-activity relationship. DNA binding properties of these alkaloids are interpreted in relation to their biological activity.