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At least 487 records · Page 27Linked to original sources
PubMed2004

A biophysical model of neuronal dendrites' integrative properties: relations to morphological data.

We used a biophysical model to probe the basic integrative properties of primate pallidal neurons in order to obtain a better understanding of Basal Ganglia physiology. The first results we present here deal mainly with the way dendritic morphology influences these properties. Neuronal morphology has been quantitatatively analyzed in 3D. Single fast excitatory synaptic inputs resulting in AMPA receptors activations have been simulated, without regenerative voltage dependent conductances. Dendrites of both pallidal segments (GPi and GPe) showed a strong dependence of the synaptic efficacy upon distance from soma, but even the most distal dendritic synaptic sites were able to substantially depolarize the cell body. The mean synaptic efficacy was the same in both populations, but the attenuation of propagated post-synaptic potentials was higher in GPi neurons. All these features were very dependent on the dendritic diameters which appear to constitute a key parameter in these neuronal populations both with respect to the integration of afferent information and to the differences between cells in performing this task.

Biophysical Phenomena↗
PubMed1995

Biophysics of the membrane interface.

It is clear that the interface is a highly complex region of the bilayer. In summary: (i) anionic lipids can interact in a stoichiometric way with charged protein residues; (ii) proteins are induced into 'molten globule' states on interaction with the membrane surface; (iii) local pH and hydration of the surface is not uniform and does not reflect the bulk properties; (iv) the contributions to the energetics of protein or peptide interaction are not well resolved and may not be readily measured; (v) as a result of electrostatic interactions between proteins and lipids, biomembranes may contain laterally separated domains that, at their interfaces, provide mismatched regions capable of permitting passage of components through the bilayer; (vi) the mode of insertion, folding and translocation may be determined directly by the surface properties of the biomembrane. Much still needs to be done to enable a complete description of the biophysics (mechanisms and energetics) of protein folding, insertion and translocation, and how this is affected by the bilayer surface, the initial site of interaction of such species. More experimental evidence, as well as theory to understand the results, is required before the measured thermodynamic parameters meet with descriptions of the various contributions for the process. Deuterium NMR is one direct and highly sensitive experimental approach to help in the understanding of such electrostatics at membrane interfaces.

Apoproteins↗
PubMed2000

Biophysical studies of the development of amyloid fibrils from a peptide fragment of cold shock protein B.

The peptide CspB-1, which represents residues 1-22 of the cold shock protein CspB from Bacillus subtilis, has been shown to form amyloid fibrils when solutions containing this peptide in aqueous (50%) acetonitrile are diluted in water [M. Gross et al. (1999) Protein Science 8, 1350-1357] We established conditions in which reproducible kinetic steps associated with the formation of these fibrils can be observed. Studies combining these conditions with a range of biophysical methods reveal that a variety of distinct events occurs during the process that results in amyloid fibrils. A CD spectrum indicative of beta structure is observed within 1 min of the solvent shift, and its intensity increases on a longer timescale in at least two kinetic phases. The characteristic wavelength shift of the amyloid-binding dye Congo Red is established within 30 min of the initiation of the aggregation process and corresponds to one of the phases observed by CD and to changes in the Fourier transform-infrared spectrum indicative of beta structure. Short fibrillar structures begin to be visible under the electron microscope after these events, and longer, well-defined amyloid fibrils are established on a timescale of hours. NMR spectroscopy shows that there are no significant changes in the concentration of monomeric species in solution during the events leading to fibril formation, but that soluble aggregates too large to be visible in NMR spectra are present throughout the process. A model for amyloid formation by this peptide is presented which is consistent with these kinetic data and with published work on a variety of disease-related systems. These findings support the concept that the ability to form amyloid fibrils is a generic property of polypeptide chains, and that the mechanism of their formation is similar for different peptides and proteins.

Amino Acid Sequence↗
PubMed2004

Biophysics of ablation: application to technology.

INTRODUCTION: The question of what happens to tissue during radiofrequency (RF) catheter ablation continues to be asked as we evolve into the use of newer delivery systems. METHODS AND RESULTS: Three assumptions are made about RF ablation. (1) Tissue injury is thermally mediated; (2) heat transfer in tissue should be a predictable biophysical phenomenon; and (3) large lesion technologies have more or less equivalent efficacies. Based on these assumptions, predictions are made and discussed. Many of the predictors were proven to be true while some surprisingly were not. CONCLUSION: In conclusion, tissue-area injury occurs reproducibly at a temperature of about 50 degrees C. Heat transfer in tissue is a predictable phenomenon. And finally, new technologies for large lesions are all effective, but greater surface area of ablation was achieved with a 10-mm tip and greater depth was achieved with a Chilli cooled ablation catheter.

Animals↗
PubMed1999

Biophysical shunt theory for neuropsychopathology: pentaphasic lipid-induced model for schizophrenia.

We propose a five-phase model for schizophrenia: (A) Imperfect diet-induced fatty acid combinations are mobilized from reservoirs during stress exposure into the bloodstream; (B) Increased brain-blood barrier permeability, with a further penetration of fat into the brain matter; (C) Rearrangement in the regional neuronal membrane fatty acids with a further physical compression of the adjacent membrane protein structures causing conformational alterations; (D) Cytokines generate further physical changes, impairing single- or multi-dispersed ion channels placed on the same neuron; (E) Ion channels are blocked, with a subsequent biophysical ion shunt-to-ion flow propagation, which results in neuronal misfiring and the appearance of schizophrenic signs and symptoms.

Biophysical Phenomena↗
PubMed2004

Biophysical constraints on the origin of leaves inferred from the fossil record.

The molecular tool kit for producing flat-bladed photosynthetic structures evolved in marine and terrestrial plants during the middle Paleozoic, but it took a further 20 million years before leaves suddenly spread throughout land floras. This delay has long been difficult to explain, given the apparent advantage of leaves for photosynthetic primary production. Theory and experiments predict that exceptionally high atmospheric CO2 levels in the middle Paleozoic delayed the origin of leaves by restricting stomatal development. This would have limited evaporative cooling, leading to lethal overheating of leaves absorbing large quantities of solar energy. Here we test the central prediction of this argument with a morphometric analysis of 300 plant fossils from major European collections. We show a 25-fold enlargement of leaf blades in two phylogenetically independent clades as atmospheric CO2 levels fell during the late Paleozoic. Furthermore, preliminary data suggest that the first abrupt increase in leaf size was accompanied by an 8-fold rise in stomatal density. These evolutionary patterns support the relaxation of biophysical constraints on leaf area predicted by theory and point to a significant role for CO2 in plant evolution.

Atmosphere↗
PubMed1990

Biophysical model of a Hebbian synapse.

We present a biophysical model of electrical and Ca(2+) dynamics following activation of N-methyl-D-aspartate (NMDA) receptors located on a dendritic spine. The model accounts for much of the phenomenology of the induction of long-term potentiation at a Hebbian synapse in hippocampal region CA1. Computer simulations suggested four important functions of spines in this Ca(2+)-dependent synaptic modification: (i) compartmentalizing transient changes in [Ca(2+)] to just those synapses that satisfy the conjunctive requirement for synaptic modification; (ii) isolating the spine head from changes in the [Ca(2+)] at the dendritic shaft; (iii) amplifying the concentration changes at those synapses; and (iv) increasing the voltage dependence of the processes underlying long term potentiation induction. This proposed role of spines in the regulation of Ca(2+) dynamics contrasts with traditional approaches to spine function that have stressed electronic properties. This model can be used to explore the computational implications of Hebbian synapses.

Animals↗
PubMed1994

Sodium channel mutations in paramyotonia congenita exhibit similar biophysical phenotypes in vitro.

Mutations in the skeletal muscle voltage-gated Na+ channel alpha-subunit have been found in patients with two distinct hereditary disorders of sarcolemmal excitation: hyperkalemic periodic paralysis (HYPP) and paramyotonia congenita (PC). Six of these mutations have been functionally expressed in a heterologous cell line (tsA201 cells) using the recombinant human skeletal muscle Na+ channel alpha-subunit cDNA hSkM1. PC mutants from diverse locations in this subunit (T1313M, L1433R, R1448H, R1448C, A1156T) all exhibit a similar disturbance in channel inactivation characterized by reduced macroscopic rate, accelerated recovery, and altered voltage dependence. PC mutants had no significant abnormality in activation. In contrast, one HYPP mutation studied (T704M) has a normal inactivation rate but exhibits shifts in the midpoints of steady-state activation and inactivation along the voltage axis. These findings help to explain the phenotypic differences between HYPP and PC at the molecular and biophysical level and contribute to our understanding of Na+ channel structure and function.

Base Sequence↗
PubMed2001

Biophysical characterization of the DNA binding domain of gpNu1, a viral DNA packaging protein.

Terminase enzymes are common to double-stranded DNA viruses. These enzymes "package" the viral genome into a pre-formed capsid. Terminase from bacteriophage lambda is composed of gpA (72.4 kDa) and gpNu1 (20.4 kDa) subunits. We have described the expression and biochemical characterization of gpNu1DeltaK100, a construct comprising the N-terminal 100 amino acids of gpNu1 (Yang, Q., de Beer, T., Woods, L., Meyer, J., Manning, M., Overduin, M., and Catalano, C. E. (1999) Biochemistry 38, 465-477). Here we present a biophysical characterization of this construct. Thermally induced loss of secondary and tertiary structures is fully reversible. Surprisingly, although loss of tertiary structure is cooperative, loss of secondary structure is non-cooperative. NMR and limited proteolysis data suggest that approximately 30 amino acids of gpNu1DeltaK100 are solvent-exposed and highly flexible. We therefore constructed gpNu1DeltaE68, a protein consisting of the N-terminal 68 residues of gpNu1. gpNu1DeltaE68 is a dimer with no evidence of dissociation or further aggregation. Thermally induced unfolding of gpNu1DeltaE68 is reversible, with concomitant loss of both secondary and tertiary structure. The melting temperature increases with increasing protein concentration, suggesting that dimerization and folding are, at least in part, coupled. The data suggest that gpNu1DeltaE68 represents the minimal DNA binding domain of gpNu1. We further suggest that the C-terminal approximately 30 residues in gpNu1DeltaK100 adopt a pseudo-stable alpha-helix that extends from the folded core of the protein. A model describing the role of this helix in the assembly of the packaging apparatus is discussed.

Binding Sites↗
PubMed2005

Biophysical comparison of BMP-2, ProBMP-2, and the free pro-peptide reveals stabilization of the pro-peptide by the mature growth factor.

Pro-forms of growth factors have received intensive scientific attention recently because in some cases different biological activities have been ascribed compared with the mature growth factors. Examples are the pro-apoptotic role of the nerve growth factor (NGF) proform (proNGF) or the latency of the transforming growth factor (TGF)-beta pro-form (proTGF-beta). To investigate a possible biological function of the pro-form of bone morphogenetic protein (BMP)-2, a member of the TGF-beta family, mature BMP-2, proBMP-2, and the isolated pro-peptide were recombinantly produced in Escherichia coli cells, and a biophysical comparison was performed. Protocols were developed that allowed efficient refolding and subsequent purification of the proteins. ProBMP-2 could be processed to an N-terminally truncated form of BMP-2, digit removed BMP-2 (drBMP-2), that possessed biological activity, i.e. it induced ectopic bone formation. Bone inducing activity was also displayed by proBMP-2. The three proteins were characterized both by fluorescence and CD spectroscopy. From these analyses, predominant beta-sheet secondary structural elements in the pro-peptide were deduced. The thermodynamic stability of the pro-peptide was determined by chemical unfolding assays. As in the case of NGF/proNGF, the mature part of BMP-2 stabilized the structure of the pro-peptide moiety. However, in contrast to NGF/proNGF, the pro-peptide did not stimulate oxidative folding of the mature part in vitro.

Animals↗
PubMed1998

Radiation-induced total-deletion mutations in the human hprt gene: a biophysical model based on random walk interphase chromatin geometry.

PURPOSE: To develop a biophysical model that explains the sizes of radiation-induced hprt deletions. METHODS: Key assumptions: (1) Deletions are produced by two DSB that are closer than an interaction distance at the time of DSB induction; (2) Interphase chromatin is modelled by a biphasic random walk distribution; and (3) Misrejoining of DSB from two separate tracks dominates at low-LET and misrejoining of DSB from a single track dominates at high-LET. RESULTS: The size spectra for radiation-induced total deletions of the hprt gene are calculated. Comparing with the results of Yamada and coworkers for gamma-irradiated human fibroblasts the study finds that an interaction distance of 0.75 microm will fit both the absolute frequency and the size spectrum of the total deletions. It is also shown that high-LET radiations produce, relatively, more total deletions of sizes below 0.5 Mb. The model predicts an essential gene to be located between 2 and 3 Mb from the hprt locus towards the centromere. Using the same assumptions and parameters as for evaluating mutation frequencies, a frequency of intra-arm chromosome deletions is calculated that is in agreement with experimental data. CONCLUSIONS: Radiation-induced total-deletion mutations of the human hprt gene and intrachange chromosome aberrations share a common mechanism for their induction.

Biophysical Phenomena↗
PubMed2006

Genomics, morphogenesis and biophysics: triangulation of Purkinje cell development.

The cerebellar Purkinje cells (P-cells) comprise an organelle that is suitable for combined analysis by morphology and genomics, using biophysical tools. In some unknown way, genomic information specifies the development of P-cells. One of us (AJP) has previously proposed that fractal processes associated with DNA are in a causal relation to the fractal properties of organelles such as P-cells (FractoGene, 2002, patent pending). This fractal postulate predicts that the dendritic arborization of P-cells will be less complex in lower order vertebrates. The prediction can be tested by systematic comparative neuroanatomy of the P-cell in species for which genome sequences permit inter-species comparison. The Fugu rubripes (Fugu), Danio rerio (Danio) and other species are lower order vertebrates for which genome sequences are available and tests could be conducted. Consistent with the fractal prediction, P-cell dendritic arbor is primitive in Fugu, being much less complex than in Mus musculus and in Homo sapiens. Genomic analysis readily identified PEP19/Pcp4, Calbindin-D28k, and GAD67 genes in Fugu and in Danio that are closely associated with P-cells in Canis familiaris, Rattus norvegicus, Mus musculus and Homo sapiens. Gene L7/Pcp2 exhibits strongest association with P-cells in higher vertebrates. L7/Pcp2 shows strong protein residue homology with genes greater than 600 residues and including 2-3 GoLoco domains, designated as having G protein signaling modulator function (AGS3-like proteins). Fugu has a short gene with a single GoLoco domain, but it has greatest homology with the AGS3-like proteins. No similar short gene is present in Danio or in Xenopus. Classical L7/Pcp2 is only detected in higher vertebrates, suggesting that it may be a marker of more recent evolutionary development of cerebellar P-cells. We expect that a new generation of data mining tools will be required to support recursive fractal geometrical, combinatorial, and neural network models of the genomic basis of morphogenesis.

Animals↗
PubMed1999

Biophysical properties and slow voltage-dependent inactivation of a sustained sodium current in entorhinal cortex layer-II principal neurons: a whole-cell and single-channel study.

The functional and biophysical properties of a sustained, or "persistent," Na(+) current (I(NaP)) responsible for the generation of subthreshold oscillatory activity in entorhinal cortex layer-II principal neurons (the "stellate cells") were investigated with whole-cell, patch-clamp experiments. Both acutely dissociated cells and slices derived from adult rat entorhinal cortex were used. I(NaP), activated by either slow voltage ramps or long-lasting depolarizing pulses, was prominent in both isolated and, especially, in situ neurons. The analysis of the gating properties of the transient Na(+) current (I(NaT)) in the same neurons revealed that the resulting time-independent "window" current (I(NaTW)) had both amplitude and voltage dependence not compatible with those of the observed I(NaP), thus implying the existence of an alternative mechanism of persistent Na(+)-current generation. The tetrodotoxin-sensitive Na(+) currents evoked by slow voltage ramps decreased in amplitude with decreasing ramp slopes, thus suggesting that a time-dependent inactivation was taking place during ramp depolarizations. When ramps were preceded by increasingly positive, long-lasting voltage prepulses, I(NaP) was progressively, and eventually completely, inactivated. The V(1/2) of I(NaP) steady state inactivation was approximately -49 mV. The time dependence of the development of the inactivation was also studied by varying the duration of the inactivating prepulse: time constants ranging from approximately 6.8 to approximately 2.6 s, depending on the voltage level, were revealed. Moreover, the activation and inactivation properties of I(NaP) were such as to generate, within a relatively broad membrane-voltage range, a really persistent window current (I(NaPW)). Significantly, I(NaPW) was maximal at about the same voltage level at which subthreshold oscillations are expressed by the stellate cells. Indeed, at -50 mV, the I(NaPW) was shown to contribute to >80% of the persistent Na(+) current that sustains the subthreshold oscillations, whereas only the remaining part can be attributed to a classical Hodgkin-Huxley I(NaTW). Finally, the single-channel bases of I(NaP) slow inactivation and I(NaPW) generation were investigated in cell-attached experiments. Both phenomena were found to be underlain by repetitive, relatively prolonged late channel openings that appeared to undergo inactivation in a nearly irreversible manner at high depolarization levels (-10 mV), but not at more negative potentials (-40 mV).

Algorithms↗
PubMed2001

Tissue engineering: the biophysical background.

Tissue engineering is the construction, repair or replacement of damaged or missing tissue in humans and other animals. This engineering may take place within the animal body or as tissue constructs to be made in a bioreactor for later grafting into the animal. The minimal set of materials for this are the appropriate types of cell. Usually, however, non-living substrata are used as well. These substrata may be nothing more than materials that bulk up any voids in the damaged tissue and provide the mechanical strength that has been lost when the tissue is damaged or removed. They may serve a similar pair of functions in the bioreactor. They can do much more in terms of pattern formation. The orientations and morphology of the cells, the arrangement of intercellular material as it is laid down and the relationships between different cell types in the repairing or construct tissue are all of importance, for these should resemble the correct normal tissue as closely as possible. Most of these requirements are ones involving pattern formation. This review discusses the various ways in which tissue pattern can be engineered chiefly from a biophysical standpoint. Unpatterned cells are effectively not tissue. This engineering includes the use of topography on the substrata, chemical patterning of adhesive and other cues for the cells, mechanical force application to cause cell orientation and appropriate synthetic responses and electrical fields. The review also discusses the methods used to impart the appropriate cues to and through the materials which are often biodegradable polymers. The article gives particular attention to regions of research and practice where the involvement of the physicist or biophysicist is of importance.

Animals↗
PubMed1996

Basic biophysical principles of resurfacing of human skin by means of the carbon dioxide laser.

This discussion analyzes the biophysical effects of superpulsed, ultrapulsed, and swept-beam carbon dioxide lasers in the removal of the outer layers of skin for the purpose of facial resurfacing. It presents the differences in mode of operation among these systems, and their comparative advantages and disadvantages. The history of laser facial resurfacing, the characteristics of an ideal resurfacing laser, the importance of transverse electromagnetic mode, principles of minimization of thermal damage, the concept of ablation threshold, and the effect of pulse duration on thermal damage to adjacent tissue are discussed. The analysis is based upon some simplifying assumptions about the structure of epidermis and dermis, and the results are compared with those from empirical measurements, presenting a rational foundation for understanding the important phenomena of laser ablation of skin.

Biophysical Phenomena↗
PubMed2004

Biophysical parameters influence actin-based movement, trajectory, and initiation in a cell-free system.

Using a biochemically complex cytoplasmic extract to reconstitute actin-based motility of Listeria monocytogenes and polystyrene beads coated with the bacterial protein ActA, we have systematically varied a series of biophysical parameters and examined their effects on initiation of motility, particle speed, speed variability, and path trajectory. Bead size had a profound effect on all aspects of motility, with increasing size causing slower, straighter movement and inhibiting symmetry-breaking. Speed also was reduced by extract dilution, by addition of methylcellulose, and paradoxically by addition of excess skeletal muscle actin, but it was enhanced by addition of nonmuscle (platelet) actin. Large, persistent individual variations in speed were observed for all conditions and their relative magnitude increased with extract dilution, indicating that persistent alterations in particle surface properties may be responsible for intrinsic speed variations. Trajectory curvature was increased for smaller beads and also for particles moving in the presence of methylcellulose or excess skeletal muscle actin. Symmetry breaking and movement initiation occurred by two distinct modes: either stochastic amplification of local variation for small beads in concentrated extracts, or gradual accumulation of strain in the actin gel for large beads in dilute extracts. Neither mode was sufficient to enable spherical particles to break symmetry in the cytoplasm of living cells.

Actins↗
PubMed1991

A proposed biophysical framework for radiation protection calculations using summation of iso-risk contributions of different radiations.

A biophysical framework for administrative radiation protection calculation using summation of iso-risk contribution of different radiation components is presented. It addresses some of the concerns with the present system but would preserve the present linear mathematical framework and hence the massive literature of numerical calculations in radiation protection.

Biophysical Phenomena↗
PubMed1997

Biophysical bases for delayed and aberrant motor development in young children with achondroplasia.

Achondroplasia, the most common skeletal dysplasia, is characterized by delayed and aberrant motoric development in childhood. Delays and aberrancy are secondary to the anatomical differences inherent in people with achondroplasia. We present a photographic essay documenting biophysical differences, aberrant pre-orthograde movement strategies, and selected adaptive techniques. A parental questionnaire assessed the presence of, predominance, and ages at which various types of pre-orthograde locomotion were observed. Fine and gross motor skills were assessed contemporaneously by use of the Denver Developmental Screening Test in 93 children with achondroplasia and were found to be more delayed than previously reported. Physicians, therapists, early-childhood educators, and parents should recognize that aberrant does not mean maladaptive and that different development is not defective development.

Achondroplasia↗