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At least 415 records · Page 23Linked to original sources
PubMed1989

Biophysical aspects of lipid interaction with mineral: liposome model studies.

The present paper reviews the use of liposomes as synthetic models for studying various biophysical aspects of matrix vesicle calcification, especially the involvement of acidic phospholipids in the nucleation and growth processes which occur during the initial stages of mineral formation in and around these membrane-bound structures. Recent results showed that acidic phospholipids incorporated into phosphatidylcholine-rich anionic liposome membranes were ineffective in initiating extraliposomal calcium phosphate precipitation from metastable solutions at physiological pH. On the contrary, certain acidic phospholipids such as phosphatidic acid and phosphatidylserine retarded the development of such precipitation when the latter was endogenously induced. The extent of inhibition correlated with the strength of the electrostatic interaction between the polar head group of the acidic phospholipid and the surface of the mineral phase. The results suggest that acidic phospholipids may play an important role in controlling the rate of early mineral development in matrix vesicle calcification.

Biophysical Phenomena↗
PubMed2003

Biophysical limits on athermal effects of RF and microwave radiation.

Using biophysical criteria, I show that continuous radiofrequency (RF) and microwave radiation with intensity less than 10 mW/cm(2) are unlikely to affect physiology significantly through athermal mechanisms. Biological systems are fundamentally noisy on the molecular scale as a consequence of thermal agitation and are noisy macroscopically as a consequence of physiological functions and animal behavior. If electromagnetic fields are to significantly affect physiology, their direct physical effect must be greater than that from the ubiquitous endogenous noise. Using that criterion, I show that none of a set of interactions of weak fields, which I argue is nearly complete on dimensional grounds, can affect biology on the molecular scale. Moreover, I conclude that such weak fields are quite unlikely to generate significant effects in their interactions with larger biological elements such as cells. In the course of that analysis, I examine important special examples of electromagnetic interactions: "direct" interactions where biology is modified simply by the motion of charged elements generated by the electric field; resonance interactions; the effects of electrostrictive forces and induced dipole moments; and modifications of radical pair recombination probabilities. In each case, I show that it is unlikely that low intensity fields can generate significant physiological consequences.

Biophysical Phenomena↗
PubMed2002

Radiation-induced chromosome aberrations: insights gained from biophysical modeling.

Enzymatic misrepair of ionizing-radiation-induced DNA damage can produce large-scale rearrangements of the genome, such as translocations and dicentrics. These and other chromosome exchange aberrations can cause major phenotypic alterations, including cell death, mutation and neoplasia. Exchange formation requires that two (or more) genomic loci come together spatially. Consequently, the surprisingly rich aberration spectra uncovered by recently developed techniques, when combined with biophysically based computer modeling, help characterize large-scale chromatin architecture in the interphase nucleus. Most results are consistent with a picture whereby chromosomes are mainly confined to territories, chromatin motion is limited, and interchromosomal interactions involve mainly territory surfaces. Aberration spectra and modeling also help characterize DNA repair/misrepair mechanisms. Quantitative results for mammalian cells are best described by a breakage-and-reunion model, suggesting that the dominant recombinational mechanism during the G(0)/G(1) phase of the cell cycle is non-homologous end-joining of radiogenic DNA double strand breaks. In turn, better mechanistic and quantitative understanding of aberration formation gives new insights into health-related applications.

Animals↗
PubMed1989

Discrimination between different types of low-level luminescence in mammalian cells: the biophysical radiation.

Cellular low-level luminescence was measured after various disintegrative processes in brain cell preparations. In addition to known origins of low-level luminescence, e.g. oxygen radical reactions or enzymatic and non-enzymatic redox systems, a further source of photon emission is reported which is independent of external oxygen, oxygen radicals and enzyme activities. Vital cells from rat brain homogenates or pig oligodendrocytes could be kept for hours at 37 degrees C without any photon emission. Only after disintegrative processes a cellular photon emission could be induced. The maximal intensity of about 400 impulses/s/mg protein and a total radiation of about 6 X 10(6) l/mg depended on the type of cells. The signal could be retained completely at 4 degrees C or in frozen samples. Heating (10 min, 90 degrees C) did not suppress the photon emission. Luminol and lucigenin did not amplify the signal as is usually observed in oxygen radical-producing cells. Non-specific radical scavengers as well as detergents suppressed the cellular photon emission completely. It is suggested that this cellular luminescence represents a biophysical radiation which originates from the interruption of an intermolecular radiationless energy transfer.

Animals↗
PubMed2003

Biosynthesis and biophysical analysis of domains of a yeast G protein-coupled receptor.

The alpha-factor receptor(Ste2p) is required for the sexual conjugation of the yeast Saccharomyces cerevisiae. Ste2p belongs to the G protein-coupled receptor (GPCR) family sharing a common heptahelical transmembrane structure. Biological synthesis of regions of Ste2p fused to a leader protein in Escherichia coli yielded milligram quantities of polypeptides that corresponded to one or two transmembrane domains. Fusion proteins were characterized by polyacrylamide gel electrophoresis, high performance liquid chromatography, and mass spectrometry. CD studies on the fusion proteins in trifluoroethanol:water mixtures indicated the existence of alpha-helical structures in the single- and the double-transmembrane domains. NMR experiments were performed in CDCl(3):CD(3)OH:H(2)O (4:4:1) on the (15)N-labeled single-transmembrane peptide showing a clear dispersion of the nitrogen-amide proton correlation cross peaks indicative of a high-purity, uniformly labeled molecule. The results indicate that single- and double-transmembrane domains of a GPCR can be produced by biosynthetic methods in quantities and purity sufficient for biophysical studies.

Amino Acid Sequence↗
PubMed1994

Biophysical studies on fragments of the alpha-factor receptor protein.

The receptor for the alpha-factor mating pheromone of the yeast Saccharomyces cerevisiae consists of 431 amino acid residues and is a member of a family of membrane proteins predicted to have seven transmembrane helices. Fragments of the receptor corresponding to two of the transmembrane helices [residues 246-269 (M6) and 273-302 (M7)], two of the interhelical loops [residues 107-125 (E2) and 191-206 (E3)], and to a portion of the carboxyl terminus [residues 350-372 (CT)] were synthesized using solid-phase methodologies and purified to near homogeneity. CD was used to characterize the secondary structure of these peptides in trifluoroethanol (TFE), in TFE/water mixtures, in sodium dodecyl sulfate (SDS), and in the presence of dimyristoyl phosphatidylcholine (DMPC) liposomes. In TFE, M6 and M7 exhibited CD spectra consistent with highly helical peptides, whereas CT was partially helical. In contrast, E2 and E3 were either disordered or aggregated in this solvent. M6 did not partition well into DMPC vesicles whereas M7 remained helical. Both M6 and M7 assumed helical conformations in 25 mM SDS. The loop peptides and the carboxyl terminus peptide were either in a beta-structure or disordered in the presence of lipid. These findings represent the first biophysical evidence for conformations assumed by specific segments of the STE2 receptor protein.

Amino Acid Sequence↗
PubMed2005

A theoretical description of elastic pillar substrates in biophysical experiments.

Arrays of elastic pillars are used in biophysical experiments as sensors for traction forces. The evaluation of the forces can be complicated if they are coupled to the pillar displacements over large distances. This is the case if many of the pillars are interconnected by elastic linkages as, for example, in fiber networks that are grown on top of pillars. To calculate the traction forces in such a network, we developed a set of nonlinear inhomogeneous equations relating the forces in the linking elements to the resulting pillar deflections. We chose a homogeneous, activated two-dimensional network of cytoskeletal actin filaments to illustrate that a pillar substrate is generally not a force sensor but a force-gradient sensor. In homogeneous networks the forces acting along the filaments can be approximated by analyzing only pillar deflections in the edge zones of the substrate and by integration over the corresponding force gradients.

Actin Cytoskeleton↗
PubMed1980

Biophysical evaluation of the tumorigenic response to implanted polymers.

An evaluation of the biophysical changes of methylcholanthrene induced tumor (M4) in laboratory animals receiving four different alloplastic implants was conducted. The implants are silicone, polyether urethane, poly(methyl methacrylate), and bioglass. The tumor was allowed to grow to a large size in 28 days and then removed by shelling it from the surrounding tissue. Three different analytic volumetric measurements were carried; size in cm3, volume in milliliters and weight in grams. Statistical analysis on the three different analytic measurements did not disclose any significant differences in tumor growth potential between the control and the experimental groups. We conclude that in this study we were unable to demonstrate any tumor "facilitation" effect by any of the implantable polymers used. Therefore, there is no contraindication in using the polymers to reconstruct defects produced by cancer ablative procedures.

Animals↗
PubMed2003

Biophysical characterization of PEI/DNA complexes.

The main goal of this study was to determine the effects of polyethylenimine (PEI) molecular weight and structure (750 kDa, 25 kDa, 2 kDa branched, and 25 kDa linear PEI) and the nitrogen/phosphate (N/P) molar ratio on the physical properties and transfection efficiencies of PEI/DNA complexes. Fourier transform infrared spectroscopy revealed that DNA remained in the B conformation when complexed to all PEIs. Unique alterations in the circular dichroism spectra of DNA were observed in the presence of each PEI, whereas differential scanning calorimetry measurements showed that all PEIs examined destabilized supercoiled DNA at N/P < 3/1, but not at higher ratios. Isothermal titration calorimetry revealed the existence of protonation changes at low ionic strength due to possible shifts in pK(a) of the ionizable groups of PEI during complex formation. Twenty-five kilodalton branched and 25 kDa linear PEI complexes showed the highest transfection efficiencies at an N/P ratio of 6:1 in COS-7 and CHO-K1 cells, respectively. These investigations have detected alterations in the physical and colloidal properties of the complexes that were sensitive to polymer structure, molecular weight, and polymer/DNA ratio, but these properties did not directly correlate with their transfection efficiencies. To further probe any possible relationship between these parameters and activity, a more refined biophysical analysis of any subpopulations in these samples that may differ in transfection activity is suggested, although the existence of such species remains unknown.

Animals↗
PubMed2005

Biophysical signatures of noncovalent aggregates formed by a glucagonlike peptide-1 analog: a prototypical example of biopharmaceutical aggregation.

LY307161 is a 31 amino acid analog of glucagonlike peptide-1(7-37)OH susceptible to physical instability associated with pharmaceutical processing. Orthogonal biophysical studies were conducted to explore the origins of this physical instability and to distinguish pharmaceutically desirable states of this aggregating peptide from undesirable ones. Equilibrium sedimentation analysis established that LY307161 exists as a monomer at pH 3, and reversibly self-associates in the pH range 7.5-10.5. Causative factors for physical instability related to lyophilization conditions were investigated. Solution pH, acetonitrile content, and concentration of the peptide prior to lyophilization each impacted physicochemical properties of the resultant powders. A comparative study of two powder samples exhibiting physicochemically disparate properties established that LY307161 forms soluble noncovalent aggregates. FT-IR analyses in the solid and solution states identified a prominent band at 1657-1659 cm(-1) attributed to alpha-helix structure. Noncovalent soluble aggregate exhibited characteristic bands at 1615 and 1698 cm(-1) indicative of intermolecular beta-sheet structure. An agitation-induced, precipitated solid form of LY307161 exhibited a different FT-IR signature indicative of a conformationally distinct species. Circular dichroism and fluorescence spectroscopy, together with dynamic light scattering measurements and dye-aggregate complexation, provided additional insights into the distinctions between aggregated and native LY307161.

Biophysical Phenomena↗
PubMed2006

Biophysical comparability of the same protein from different manufacturers: a case study using Epoetin alfa from Epogen and Eprex.

This study focuses on the development and application of biophysical methodology to characterize conformations of Epogen and Eprex, the injectable formulations of recombinant human Epoetin alfa produced by different manufacturers and commonly used for the treatment of renal anemia. In these studies Eprex, from prefilled syringes, and Epogen bulk product formulated in a buffer similar to the Eprex formulation, were purified by anion-exchange chromatography. Analytical ultracentrifugation studies of the purified main peak from each sample demonstrated that Epogen contains a single component with an s value of 2.51 while Eprex contains a single component with the same molecular weight but with an s value of 2.44 suggesting a slight difference in hydrodynamic structure. The degree of alpha-helicity was compared by far-UV circular dichroism and shown to contain slight differences. Intrinsic tryptophan fluorescence and near-UV circular dichroism were assessed and demonstrated additional differences between the proteins. Finally, the global stability of the proteins was monitored using thermal unfolding monitored by far-UV circular dichroism. The Epoetin alfa of Epogen demonstrated complete reversibility while the Epoetin alfa purified from Eprex demonstrated only 80%-85% thermal reversibility when heated to 100 degrees C. Together the data indicate that the proteins are not structurally identical.

Algorithms↗
PubMed1995

A biophysical model of passive and polarized active transport processes in Caco-2 cells: approaches to uncoupling apical and basolateral membrane events in the intact cell.

This report is aimed at the biophysical modeling of transmembrane events involving a passive diffusion and directional pumplike mechanism at the apical (AP) and basolateral (BL) membranes of cultured cell monolayers. The essence of the model is based on experimental evidences for the existence of a saturable, apically polarized transport system in Caco-2 cells for peptides which hindered apical to basolateral flux, enhanced basolateral to apical flux, and showed substrate specificity. This system was further inhibited by verapamil, suggesting some homology with P-glycoprotein, the principal mediator of drug resistance in multidrug resistant cancer cells. Preliminary evidence was also obtained suggesting an additional polarized uptake system for the same peptides in the basolateral membrane. Upon saturation and/or inhibition of the active transport mechanisms with verapamil, the peptide fluxes in apical-to-basolateral direction and the basolateral-to-apical direction converged and became controlled by the passive mechanism. Since the intent of the modeling was to provide useful templates for the design of probing experiments and to delineate and quantify mass transfer mechanisms at the AP and BL membranes and their interrelationships, theoretical equations were developed for a host of kinetic boundary conditions: (a) AP-->BL and BL-->AP transfluxes, (b) bidirectional effluxes from substrate-preloaded cells, (c) undirectional efflux across the AP or BL membrane from preloaded cells, and (d) uptake kinetics via the AP or BL membrane leading to equilibrium. Furthermore, flux expressions were reduced to membrane permeability coefficients to accommodate passive diffusion, saturation, inhibition, and directionality. The diffusional mass transport resistances of the aqueous boundary layers and microporous filter support of the cell monolayer were necessarily included.

Amino Acid Sequence↗
PubMed1995

Biophysical models as an approach to study passive absorption in drug development: 6-fluoroquinolones.

A preliminary study attempting to assess and explain the intestinal absorption of a series of antibacterial 7-piperazinyl-6-fluoroquinolones is presented. The synthesis, n-octanol partition coefficients, intrinsic rat gut in situ absorption rate constants, and in vitro antibacterial activity data found for these homologous compounds are described. A fluorimetric, reverse-phase HPLC method was performed for the quantification of the quinolones in absorption and partition samples. Equations based on two classic biophysical absorption models are given for predicting the intrinsic absorption features of the series according to the partition data or merely single structural parameters. In situ absorption rate constants were found to increase by a factor of 9.7-13.5 for moderately lipophilic derivatives relative to the simplest compound, while antibacterial activity decreased only by a factor of 4. In vivo absorption tests with two representative members of the series were carried out and the results showed a good accordance with those found in situ. This makes these compounds or related ones with similar partition features excellent candidates for further pharmacokinetic and pharmacological testing. The study can serve as an example of how to prevent potential absorption problems associated with the development of new drugs.

Administration, Oral↗
PubMed2003

Endurance training alters the biophysical properties of hindlimb motoneurons in rats.

The purpose of the study was to determine the effect of daily endurance treadmill training (2 h/day, 30 m/min) on motoneuron biophysical properties. Electrophysiological properties of tibial motoneurons were measured in situ in anesthetized (ketamine/xylazine) control and trained rats using sharp glass microelectrodes. Motoneurons from trained rats had significantly hyperpolarized resting membrane potentials and spike trigger levels, and faster antidromic spike rise-times. "Fast" motoneurons (after-hyperpolarization half-decay time <20 ms) in trained rats also had a significantly larger mean cell capacitance than those in control rats, suggesting that they were larger, although this had no effect on indices of excitability (rheobase, cell input resistance). Motoneurons are thus targets for activity-induced adaptations, which may have clinical significance for the role of physical activity as a therapeutic modality in cases of neurological deficit. The specific adaptations noted, which reflect alterations in ionic conductances, may serve to offset decreases in membrane excitability that occur during sustained excitation.

Action Potentials↗
PubMed2006

A biophysical model of the male urethra: comparing viscoelastic properties of polyvinyl alcohol urethras to male pig urethras.

AIMS: We aim at developing a non-invasive method for grading and diagnosing urinary bladder outlet obstruction, based on noise recording with a perineal contact microphone during voiding. We found that the noise production during voiding depends amongst others on the viscoelastic properties of the urethral wall. To further test our method, we need a realistic biophysical model of the male urethra. METHODS: We made various model urethras with different viscoelastic properties from a 10% aqueous solution of polyvinyl alcohol cryogel. We measured the viscoelastic properties of each model and compared them to those of the male pig urethra. The male pig urethra was used, as it is physiologically comparable to the human male urethra. The viscoelastic properties of both model and pig urethras were measured by applying strain to the urethral wall in a stepwise manner and recording the pressure response. We fitted the step-response of a mechanical model to this pressure response and derived the viscoelastic properties from the coefficients of this response. RESULTS: A uniform model urethra that was freeze-thawed three times, with a Y-shaped flow channel was found to best represent the male pig urethra. CONCLUSIONS: We consider the three times freeze-thawed model urethra with a Y-shaped flow channel the best model of the human male urethra. And we therefore use this model urethra for studying the relation between noise recording during urine flow and the degree of bladder outlet obstruction.

Animals↗
PubMed1997

Reliability concept as a trend in biophysics of aging.

The vitality of a living system is determined by the reliability characteristics of its functional elements at different organizational levels--from enzymes up to the organism as a whole. The new field of biophysics, in dealing with the problem of reliability, incorporates theoretical and experimental studies on quantitative characteristics and mechanisms of failure and renewal processes in biological systems. It also includes the elaboration of methods for testing the reliability and predicting the failures in biological systems. Apart from the formal fitting to the mortality data, the theory of reliability can serve as an investigative approach for searching for realistic mechanisms of aging.

Aging↗
PubMed1998

Biophysical linkage between MRI and EEG amplitude in closed head injury.

Nuclear magnetic resonance of brain water proton (1H) T2 relaxation times and measures of absolute amplitude of EEG were obtained from 19 closed head injured patients. The relationship between EEG and T2 relaxation time differed as a function of both EEG frequency and gray matter versus white matter. White matter T2 relaxation time was positively correlated with increased EEG amplitude in the delta frequency band (0.5-3.5 Hz). In contrast, lengthened gray matter T2 relaxation time was inversely correlated with EEG amplitude in the alpha and beta frequency bands (7-22 Hz). These findings are consistent with clinical EEG studies in which white matter lesions are related to increased EEG delta amplitude and gray matter lesions are related to decreased EEG alpha and beta frequency amplitude. Estimates of the severity of injury were obtained by neuropsychological measurements, in which lengthened T2 relaxation times in both the neocortical gray and white matter were correlated with diminished cognitive function. Decreased EEG beta and alpha amplitude and increased EEG delta amplitude were also correlated with diminished cognitive function. The findings imply a biophysical linkage between the state of protein-lipid structures of the brain as measured by the MRI and the scalp-recorded EEG.

Adult↗
PubMed2006

The biophysics of T lymphocyte activation in vitro and in vivo.

T cell activation is crucial for the development of specific immune reactions. It requires physical contact between T cells and antigen-presenting cells (APC). Since these cells are initially located at distinct positions in the body, they have to migrate and find each other within secondary lymphoid organs. After encountering each other both cells have to maintain a close membrane contact sufficiently long to ensure successful signaling. Thus, there is the necessity to temporarily synchronize the motile behavior of these cells. Initially, it had been proposed that during antigen recognition, T cells receive a stop signal and maintain a stable contact with APC for several hours when an appropriate APC has been encountered. However, direct cell observation via time-lapse microscopy in vitro and in vivo has revealed a different picture. While long contacts can be observed, many interactions appear to be very short and sequential despite efficient signaling. Thus, two concepts addressing the biophysics of T cell activation have emerged. The single encounter model proposes that after a period of dynamic searching, a T cell stops to interact with one appropriately presenting APC until signaling is completed. The serial encounter model suggests that T cells are able to collect a series of short signals by different APC until a critical activation threshold is achieved. Future research needs to clarify the relative importance of short and dynamic versus long-lived T cell-APC encounters for the outcome of T cell activation. Furthermore, a thorough understanding of the molecular events underlying the observed complex motility patterns will make these phenomena amenable for intervention, which might result in the identification of new types of immune modulating drugs.

Biophysical Phenomena↗