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At least 217 records · Page 12Linked to original sources
PubMed1999

Biophysical integration of effects of epidermal growth factor and fibronectin on fibroblast migration.

Cell migration is regulated simultaneously by growth factors and extracellular matrix molecules. Although information is continually increasing regarding the relevant signaling pathways, there exists little understanding concerning how these pathways integrate to produce the biophysical processes that govern locomotion. Herein, we report the effects of epidermal growth factor (EGF) and fibronectin (Fn) on multiple facets of fibroblast motility: locomotion speed, membrane extension and retraction activity, and adhesion. A surprising finding is that EGF can either decrease or increase locomotion speed depending on the surface Fn concentration, despite EGF diminishing global cell adhesion at all Fn concentrations. At the same time, the effect of EGF on membrane activity varies from negative to positive to no-effect as Fn concentration and adhesion range from low to high. Taking these effects together, we find that EGF and Fn regulate fibroblast migration speed through integration of the processes of membrane extension, attachment, and detachment, with each of these processes being rate-limiting for locomotion in sequential regimes of increasing adhesivity. Thus, distinct biophysical processes are shown to integrate for overall cell migration responses to growth factor and extracellular matrix stimuli.

Animals↗
PubMed2002

Biophysical study of a molecular intermediate preceding collapse of tight couple and Kaltschmidt-Wittmann ribosomes.

In previous works we evidenced, by different biophysical approaches, two levels of structural organization in Escherichia coli ribosomal particles. Thermal treatment up to a defined and non-denaturing temperature causes demolition of only one level of structural complexity. By consequence the ribosomal particle exists in an intermediate state between the native form and the completely collapsed one. In this communication we report on a structural comparison of this intermediate state in Kaltschmidt-Wittmann (LC) and 'tight couple' (TC) ribosomes. Three different biophysical approaches were adopted: dielectric spectroscopy, fluorescence and light scattering. Differential responses to thermal treatment are evidenced in the two ribosomal species. In particular TC show a more compact structure and the overall particle population is more homogeneous than LC in the native state. On the other hand, LC particles after thermal treatment undergo major alterations of geometry and/or phenomena of supra-particle aggregation.

Binding Sites↗
PubMed1997

Contrasting biophysical and pharmacological properties of T-type and R-type calcium channels.

In contrast to other kinds of voltage-gated Ca2+ channels, the underlying molecular basis of T-type and R-type channels is not well-understood. To facilitate comparisons with cloned Ca2+ channel subunits, we have carried out a systematic analysis of the properties of T-type currents in undifferentiated NG108-15 cells and R-type currents in cerebellar granule neurons. Marked differences were found in their biophysical and pharmacological features under identical recording conditions. T-type channels became activated at potentials approximately 25 mV more negative than R-type channels; however, T-type channels required potentials approximately 15 mV less negative than R-type channels to be available. Accordingly, T-type channels display a much larger overlap between the curves describing inactivation and activation, making them more suitable for generating sustained Ca2+ entry in support of secretion or pacemaker activity. In contrast, R-type channels are not equipped to provide a steady current, but are very capable of supplying transient surges of Ca2+ influx. In response to a series of increasingly strong depolarizations T-type and R-type Ca2+ channels gave rise to very different kinetic patterns. T-type current records crossed each other in a characteristic pattern not found for R-type currents. These biophysical distinctions were independent of absolute membrane potential and were, therefore, complementary to the conventional categorization of T- and R-type Ca2+ channels as low- and high-voltage activated. R-type channels deactivated approximately eight-fold more quickly than T-type channels, with clear consequences for the generation of divalent cation influx during simulated action potentials. Pharmacological comparisons revealed additional contrasts. R-type current was responsive to block by omega-Aga IIIA but not nimodipine, while the opposite was true for T-type current. Both channel types were potently inhibited by the non-dihydropyridine compound mibefradil. In all respects examined, R-type currents were similar to currents derived from expression of the alpha1E subunit whereas T-type currents were not.

Animals↗
PubMed1997

Role of lipid-induced changes in plasma membrane in the biophysical shunt theory of psychopathology.

The existence of a lipid factor that either causes faulty lipid metabolism or directly contributes to the emergence of a biophysical shunt in neuronal membrane ionic flow propagation is proposed. The neuronal membrane contains a remarkable amount of phospholipids, glycolipids and cholesterol. It is assumed that, under certain unfavorable intrinsic states, the plasma membrane's lipid order and composition and, consequently, its cholesterol-to-phospholipid ratio, may change. This, in turn, may significantly modify membrane fluidity, altering the essential physical properties in the affected portions of the membrane and causing a disarray in the adjacent ion channels, leading to the establishment of a biophysical shunt in a loop-like operation, forming the basis for a variety of mental disorders. The present model offers a diet-induced lipid correction for the relief of psychopathological problems.

Animals↗
PubMed1999

Validation of a biophysical drug absorption model by the PATQSAR system.

Absorption rate constants (in situ rat gut technique) and in vitro antibacterial activities of twenty fluoroquinolones have been evaluated. A biophysical model that relates the absorption of the compounds with their lipophilicity was fitted. The model considers the absorption process from the intestinal lumen as the sum of two resistances in series: aqueous diffusional barrier and lipoidal membrane. Even if partitioning into the membrane and membrane diffusion are both enhanced for lipophilic compounds, the absorption rate constant is limited by the aqueous diffusion. To estimate the influence of structural modifications on each property and to establish the role of lipophilicity in controlling in situ absorption and in vitro antibacterial activity, the PATQSAR search system is used to construct structure-property relationships. The structural models, which explain 99% of the total variance of each physicochemical property and 96% of each in vitro biological activity, provide an explicit and precise interpretation of lipophilicity, absorption, and antimicrobial activity. The results confirm the important role of lipophilicity in controlling absorption, as pointed out by the biophysical model for the piperazinyl series, and suggest the introduction of electronic factors in order to extend the model to heterologues. They also justify the mechanism by which quinolones are assumed to induce antibacterial activity.

Algorithms↗
PubMed1999

Direct biophysical characterization of human apolipoprotein A-1 in ISCOMs.

Human apolipoprotein A-1 was formulated in "Immune Stimulating Complexes" (ISCOMs). The structure of the protein in ISCOMs was examined directly using several biophysical techniques including Fourier transform infrared (FTIR) spectroscopy, near UV circular dichroism (CD), and fluorescence spectroscopy. Amide I FTIR data indicate that human apolipoprotein A-1 displays a slightly increased alpha-helical content after its incorporation into ISCOMs. Near UV CD and tryptophan fluorescence data suggest that association with ISCOMs results in the tryptophan residues of the protein experiencing a relatively hydrophobic environment, motional restriction, and local electrostatic interactions. These observations are consistent with an increased order in the protein structure upon incorporation in ISCOMs. In addition, biomolecular interaction analysis (BIA), based on surface plasmon resonance (SPR) measurements, suggests that the binding affinity of human apolipoprotein A-1 to a monoclonal anti-human apolipoprotein A-1 antibody is moderately decreased (by 20%) after its incorporation into ISCOMs. This study demonstrates that these biophysical techniques can be used to noninvasively monitor integrity of or changes in secondary and tertiary structure of proteins within the ISCOM particles without the need for protein extraction.

Apolipoprotein A-I↗
PubMed2002

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.

Animals↗
PubMed2005

Missense meanderings in sequence space: a biophysical view of protein evolution.

Proteins are finicky molecules; they are barely stable and are prone to aggregate, but they must function in a crowded environment that is full of degradative enzymes bent on their destruction. It is no surprise that many common diseases are due to missense mutations that affect protein stability and aggregation. Here we review the literature on biophysics as it relates to molecular evolution, focusing on how protein stability and aggregation affect organismal fitness. We then advance a biophysical model of protein evolution that helps us to understand phenomena that range from the dynamics of molecular adaptation to the clock-like rate of protein evolution.

Adaptation, Biological↗
PubMed1998

Composition and biophysical properties of myelin lipid define the neurological defects in galactocerebroside- and sulfatide-deficient mice.

Oligodendrocytes and Schwann cell-specific proteins are assembled with a highly ordered membrane lipid bilayer to the myelin sheath of axons, which functions as an insulator and allows rapid saltatory conduction. We approached the question of the function of the CNS and PNS myelin-specific galactospingolipids cerebrosides and sulfatides by generating a ceramide galactosyltransferase null allelic mouse line (cgt-/-). Galactocerebroside- and sulfatide-deficient myelin loses its insulating properties and causes a severe dysmyelinosis that is incompatible with life. Here, we describe the biochemical and biophysical analysis of the myelin lipid bilayer of cgt-/- mice. The lipid composition of CNS and PNS myelin of cgt-/- mice is seriously perturbed and the sphingolipid biosynthetic pathway altered. Nonhydroxy and hydroxy fatty acid-substituted glycosylceramides (GlcC) are synthesized by oligodendrocytes and sulfated GlcC in addition in Schwann cells. The monogalactosyldiglyceride fraction is missing in the cgt-/- mouse. This new lipid composition can be correlated with the biophysical properties of the myelin sheath. The deficiency of galactocerebrosides and sulfatides leads to an increased fluidity, permeability, and impaired packing of the myelin lipid bilayer of the internodal membrane system. The loss of the two glycosphingolipid classes causes the breakdown of saltatory conductance of myelinated axons in the cgt-/- mouse.

Animals↗
PubMed2002

Biophysical behavior of Scomberoides commersonianus skin collagen.

Some biophysical characteristics of the skin collagen from Scomberoides commersonianus were measured and compared to those of rat tail tendon. Stress-strain data indicate that the strain at break as well as the tensile strength of the fish skin without scales increased significantly. The maximum tension in case of rat skin is at least a factor of two higher than that observed in fish skin. The much lower hydrothermal isometric tension measurements observed in fish skin are attributable to a lesser number of heat stable crosslinks. Stress relaxation measurements in the fish skin indicate that more than one relaxation process may be involved in the stabilization of collagenous matrix. The observed differences in the biophysical behavior of fish skin may well arise from combination of changes in extent of hydroxylation of proline in collagen synthesis, hydrogen bond network and fibril orientation as compared to rat tail tendon.

Animals↗
PubMed1989

Biophysical characterisation of diagnostic ultrasound equipment--preliminary results.

The use of diagnostic ultrasound can be justified if it can be shown to provide only negligible or small risk while giving good benefit to the patient. In the absence of biological evidence, one way of assessing a new (or existing) piece of diagnostic equipment would be to predict the biophysical changes (i.e. heat and cavitation) that may be produced by its ultrasonic fields in tissue. An assessment of risk may then be made from our knowledge of thermal and cavitational biology. To this end, this study has sought to measure temperature rise, bubble formation, sonoluminescence and acoustic streaming arising from clinical transducers that have been carefully calibrated using a Beam Calibrator, and to determine whether there is good correlation between measured acoustic parameters in water and any of these biophysical characteristics. The results are inconclusive.

Acoustics↗
PubMed1990

On the biophysical interpretation of the mathematical product of dose and relative biological effectiveness.

The mathematical product of dose and relative biological effectiveness (DR) is commonly used empirically as the 'effective' dose of radiations. It is often interpreted as the equivalent dose of a reference radiation, such that the individual DRs of the radiation components are summed like physical doses in a mixture of radiations with different RBE values. It is shown that such a physical interpretation of DR would be both mathematically and logically inconsistent unless the action of each radiation has a constant RBE value for all end-effects. This is contrary to general experimental findings. Based on the isoeffect biological connotation in the definition of RBE, a biophysical interpretation is being introduced in this paper in which DR is always interpreted with respect to a particular end-effect on which the RBE value is evaluated, somewhat similar to having an extra biological dimension. Hence, only DRs evaluated for the same end-effect can be meaningfully computed together in a mixture. From the empirical results of radiobiological experiments using mixtures of radiations of different qualities, DRs of radiation components are shown to be additive in a mixture just like physical doses. A convenient linear computation framework is, therefore, available for the use of DRs in the empirical calculation of effect of mixtures of radiations of different qualities. The bearing of this biophysical interpretation of DR on radiation protection and treatment planning is discussed.

Biophysical Phenomena↗
PubMed2004

Biochemical, biophysical and preliminary X-ray crystallographic analyses of the fusion core of Sendai virus F protein.

It is emerging that enveloped viruses may adopt a unique entry/fusion mechanism; in paramyxoviruses, including Sendai virus (SeV), the attachment protein HN (or its homologue H or G) binds a cellular receptor which triggers conformational changes of its fusion protein, F. There are at least three conformations of the F protein in the current fusion model: the pre-fusion native conformation, the pre-hairpin intermediate conformation and the post-fusion coiled-coil conformation. The fusion mechanism of SeV, a member of the Paramyxoviridae family, has been well established and several structural and functional domains or modules have been proposed from studies of its F protein. However, biochemical and biophysical studies of the heptad-repeat (HR) regions (HR1 and HR2) have not been systematically carried out. HR1 and HR2 strongly interact with each other to form a stable six-helix coiled-coil bundle as the post-fusion conformation. In this study, a single-chain HR1-linker-HR2 protein of SeV was prepared in an Escherichia coli expression system and biochemical and biophysical analyses showed it to form a typical six-helix coiled-coil bundle; its trigonal crystals diffracted X-rays to 2.5 A resolution. The crystal structure will help to reveal the structural requirements of the post-fusion coiled-coil conformation of SeV F protein.

Amino Acid Sequence↗
PubMed2005

Biophysical mechanisms and essential topography of directionally selective subunits in rabbit's retina.

We commemorate the 40th anniversary of the classical study undertaken by Barlow-Levick with a new challenge: to show how direction selectivity in the dendritic plexus of starburst amacrine cells is being computed. In the rabbit retina, although the cellular locus of direction selectivity is known to occur predominantly in the dendrites of starburst amacrine cells, the biophysical mechanism by which this takes place and its essential topography are yet to be specified with precision. A cotransmission model, involving a conjoint release of excitation/inhibition (i.e., a bisynaptic relay of endogenous ACh and GABA) from the distal varicosities of individual starburst amacrines, will be non-diphasic when the vesicular release of Ach and the non-vesicular, carrier-mediated release of GABA by transporters in the anterograde direction are preferentially suppressed by a negative feedback mechanism involving autoreceptors. Such biophysical mechanisms, including the asymmetric distribution of chloride cotransporters, explain somatofugal motion bias in starburst amacrine cells leading to autonomous functioning "subunits" that underlie the formation of directional selectivity. However, the functional independence of starburst amacrine cell "subunits" is partly a question of their network organization. The topography of directionally selective "subunits" resides in the plexus of crisscrossing dendrites of juxtaposed starburst amacrines, consisting of (i) serial synapses of three or more starburst amacrines and a ON-OFF directionally selective ganglion cell; (ii) a synaptic couplet between two starburst amacrines; and (iii) a conventional synapse between a starburst amacrine and a ON-OFF directionally selective ganglion cell. Cholinergic and GABAergic monosynaptic interactions between starburst amacrine cells, including glutamatergic interactions with cone bipolar cells, are involved in the primary circuit underlying directional selectivity. Furthermore, the secondary circuit underlying directional selectivity, consists of starburst amacrine cells and cone bipolar cells arranged in a "push-pull" configuration, interacting synaptically onto ON-OFF directionally selective ganglion cells.

Acetylcholine↗
PubMed2005

Hypoxia alters biophysical properties of endothelial cells via p38 MAPK- and Rho kinase-dependent pathways.

Hypoxia alters the barrier function of the endothelial cells that line the pulmonary vasculature, but underlying biophysical mechanisms remain unclear. Using rat pulmonary microvascular endothelial cells (RPMEC) in culture, we report herein changes in biophysical properties, both in space and in time, that occur in response to hypoxia. We address also the molecular basis of these changes. At the level of the single cell, we measured cell stiffness, the distribution of traction forces exerted by the cell on its substrate, and spontaneous nanoscale motions of microbeads tightly bound to the cytoskeleton (CSK). Hypoxia increased cell stiffness and traction forces by a mechanism that was dependent on the activation of Rho kinase. These changes were followed by p38-mediated decreases in spontaneous bead motions, indicating stabilization of local cellular-extracellular matrix (ECM) tethering interactions. Cells overexpressing phospho-mimicking small heat shock protein (HSP27-PM), a downstream effector of p38, exhibited decreases in spontaneous bead motions that correlated with increases in actin polymerization in these cells. Together, these findings suggest that hypoxia differentially regulates endothelial cell contraction and cellular-ECM adhesion.

Animals↗
PubMed2002

Invited review: biophysical properties of sodium channels in lung alveolar epithelial cells.

Amiloride-sensitive sodium channels in the lung play an important role in lung fluid balance. Particularly in the alveoli, sodium transport is closely regulated to maintain an appropriate fluid layer on the surface of the alveoli. Alveolar type II cells appear to play an important role in this sodium transport, with the role of alveolar type I cells being less clear. In alveolar type II cells, there are a variety of different amiloride-sensitive, sodium-permeable channels. This significant diversity appears to play a role in both normal lung physiology and in pathological states. In many epithelial tissues, amiloride-sensitive epithelial sodium channels (ENaC) are formed from three subunit proteins, designated alpha-, beta-, and gamma-ENaC. At least part of the diversity of sodium-permeable channels in lung arises from the assembling of different combinations of these subunits to form channels with different biophysical properties and different mechanisms for regulation. This leads to epithelial tissue in the lung, which has enormous flexibility to alter the magnitude and regulation of salt and water transport. In this review, we discuss the biophysical properties and occurrence of these various channels and some of the mechanisms for their regulation.

Animals↗
PubMed2000

Biophysical assessment of persistent effects of moisturizers after their daily applications: evaluation of corneotherapy.

BACKGROUND: Although effective moisturizers can improve xerotic skin changes immediately, their effects are only transient, because the materials applied to the stratum corneum (SC) are easily shed from the skin surface by the daily desquamation process. However, there are a few lines of clinical as well as experimental evidence suggesting that, once application of effective moisturizers is repeated daily, they may produce persistent effects without being influenced by the desquamation of the skin surface. If we can expect such pharmacological effects by simple repeated applications of moisturizers on the skin surface, it will provide a great motivation for the introduction of corneotherapy into the treatment of xerotic skin problems. OBJECTIVE: This study was designed not only to confirm the feasibility of corneotherapy but to propose a practical method to assess such long-lasting effects of moisturizers by using biophysical methods. METHODS: We conducted applications of various moisturizers twice daily to different areas of the flexor surface of the forearms for the initial 5 days of the first week. Thereafter, we performed biophysical measurements of the SC of these areas in the second week, namely 3, 5 and 7 days after their last applications. RESULTS: Daily repeated applications of moisturizers did not induce any change in the water barrier function of the SC or in the size of desquamating corneocytes, a parameter for turnover rate of the SC. However, they substantially increased high-frequency conductance, a parameter for the hydration state of the skin surface, for several days in both normal individuals and patients with atopic xerosis, although the lasting effects were shorter in the latter. The obtained data enabled us to rank the efficacy of moisturizers either according to the duration of the lasting effects or the magnitude of an increase in the hydration levels of the SC. CONCLUSION: The present results confirmed the feasibility of corneotherapy, in which even simple application of moisturizers targeted at the SC can produce unexpected persistent clinical effects after their repeated treatments. The method described in this study constitutes a practical assay system to evaluate the efficacy of topical agents used for dry skin problems objectively and quantitatively.

Adult↗
PubMed1994

Effects of fluid volume changes during hemodialysis on the biophysical parameters of the skin.

Water plays an important role in maintaining skin suppleness and elasticity. We used hemodialysis as a model to investigate the effects on biophysical properties of the skin induced by removal of fluids and water from the body. The following parameters have been investigated before and immediately after a hemodialysis session: body weight, skin elasticity and distensibility, skin hydration, transepidermal water loss (TEWL) and skin thickness. A significant decrease was recorded after treatment in body weight, skin thickness (p < 0.01) and skin elasticity (p < 0.01). Significant linear correlations were found between stratum corneum water content, skin distensibility and TEWL. The data reveal that rapid removal of body fluids influences skin biophysical properties: early changes in skin thickness and ground substance occur in the dermis and affect mechanical properties of the skin. The decrease in water content in the upper layers of the skin occurs at a later stage and influences skin hydration rather than TEWL. This model is a useful tool to investigate water kinetics through the skin.

Biophysical Phenomena↗