Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Biophysics”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 469 records · Page 26Linked to original sources
PubMed2002

Biophysical mechanisms of phospholipase A2 activation and their use in liposome-based drug delivery.

Secretory phospholipase A2 (PLA2) is a ubiquitous water-soluble enzyme found in venom, pancreatic, and cancerous fluid. It is also known to play a role in membrane remodeling processes as well as in cellular signaling cascades. PLA2 is interfacially active and functions mainly on organized types of substrate, e.g. micelles and lipid bilayers. Hence the activity of the enzyme is modulated by the lateral organization and the physical properties of the substrate, in particular the structure in the nanometer range. The evidence for nano-scale structure and lipid domains in bilayers is briefly reviewed. Results obtained from a variety of experimental and theoretical studies of PLA2 activity on lipid-bilayer substrates are then presented which provide insight into the biophysical mechanisms of PLA2 activation on lipid bilayers and liposomes of different composition. The insight into these mechanisms has been used to propose a novel principle for liposomal drug targeting, release, and absorption triggered by secretory PLA2.

Animals↗
PubMed2002

Role of sphingomyelinase and ceramide in modulating rafts: do biophysical properties determine biologic outcome?

Recent biophysical data suggest that the properties of ceramide observed in model membranes may apply to biological systems. In particular, the ability of ceramide to form microdomains, which coalesce into larger platforms or macrodomains, appears to be important for some cellular signaling processes. Several laboratories have now demonstrated similar reorganization of plasma membrane sphingolipid rafts, via ceramide generation, into macrodomains. This event appeared necessary for signaling upon activation of a specific set of cell surface receptors. In this article, we review the properties and functions of rafts, and the role of sphingomyelinase and ceramide in the biogenesis and re-modeling of these rafts. As clustering of some cell surface receptors in these domains may be critical for signal transduction, we propose a new model for transmembrane signal transmission.

Animals↗
PubMed2001

Acute and chronic changes of the apparent diffusion coefficient in neurological disorders--biophysical mechanisms and possible underlying histopathology.

Diffusion-weighted imaging (DWI) of the brain has become a valuable tool for the reliable detection and diagnosis of several neurological disorders. Although DWI is in wide use in daily practice, the underlying biophysical mechanisms that contribute to changes in the apparent diffusion coefficient (ADC) are still under discussion. Alterations in the apparent water diffusion rate reflect pathological changes in the brain tissue state, via changes in the diffusion characteristics of the intra- and extra-cellular water compartments including restricted diffusion, water exchange across permeable boundaries, the concept of the extra-cellular tortuosity and the intra- and extra-cellular volume fraction. A reduction of the ADC has been detected in acute neurological diseases, while disease states associated with dominant acute vasogenic edema formation or chronic tissue destruction usually show elevations of the ADC. Compromise of energy metabolism is likely to contribute to a reduction of the ADC while already minor structural disintegration may contribute to elevations of the ADC.

Acute Disease↗
PubMed1998

A biophysical model for the developmental time course of retinal orientation selectivity.

A quantitative study of the time course of development of the percentage of orientationally selective and isotropic ganglion cells in turtle retina has recently been performed. This study revealed that as soon as ganglion cells start responding to light, a large percentage of them are selective to the orientations of moving visual stimuli. This percentage decreases with age to reach a minimum around hatching, increases dramatically after birth and finally, decreases again following the first month of life to reach adult level. Concomitantly, the percentage of cells responding isotropically to the orientation of elongated stimuli increases monotonically until about 30 days after birth, stabilizing afterwards. To account for both time courses, we propose a biophysical model implementing features ubiquitous to developing vertebrate retinas. These features include early dendritic and synaptic spatial polarization, dendritic growth, and waves of activity generated spontaneously or by visual stimulation sweeping across the inner plexiform layer (IPL). The model also assumes a physiologically plausible Hebbian rule, which includes long-term potentiation and depression. Computer simulations of this model yield good fits of the data. The quality of these fits confirms and extends results from an earlier model using computationally-simple mechanisms, which suggested that early dendritic polarization might be the seed for mature orientation selectivity.

Animals↗
PubMedDate not supplied

The diameter-cube hypothesis: a new biophysical model of aneurysm rupture.

BACKGROUND: Recent discussions on the relationship between intracranial aneurysm diameter and rupture probability have focused on the presence of an apparent critical diameter of 10 mm for aneurysm rupture. Despite the fact that many investigators have argued against the existence of this critical diameter, no one has yet proposed a viable alternative concept. In this report we present a scientifically rigorous alternative concept, that the size-specific rupture probability (RP) of an aneurysm varies as the third power of the aneurysm diameter. METHODS: We utilized a new biophysical model of aneurysm rupture that predicts the relationship between the size-specific rupture probability of an aneurysm and the diameter (D) to be RP = kD(3). We tested this hypothesis against data from two autopsy studies and one large clinical aneurysm study. Subsequently, using this D(3) hypothesis and the different size distributions of aneurysms in the study populations, we predicted the variation of cumulative rupture probability (CRP) with diameter for each population. RESULTS: Data from the autopsy studies supported the diameter-cube hypothesis, with the log-log plots of size-specific rupture probability versus aneurysm diameter from the two autopsy series yielding lines with slopes 3.54 (R(2) = 0.61, p < 0.12) and 3.05 (R(2) = 0.98, p << 0.001). Plots of cumulative rupture probability versus diameter were determined to be sensitive to the size distributions of the unruptured aneurysms in the population. Furthermore, none of the CRP plots showed evidence of a critical diameter for aneurysm rupture. CONCLUSIONS: RP varies as the third power of aneurysm diameter, a relationship that predicts a continuous increase in RP with increasing size rather than the existence of a threshold diameter that separates low- from high-risk aneurysms. Accordingly, all aneurysms have finite risk for rupture and deserve consideration for treatment. Much of the current controversy regarding the relationship between rupture rates and diameter is a result of different size distributions in study populations rather than differences in aneurysm biology.

Aneurysm, Ruptured↗
PubMed2001

Cationic lipid-DNA complexes in gene delivery: from biophysics to biological applications.

Great expectations from the application of gene therapy approaches to human disease have been impaired by the unsatisfactory clinical progress observed. Among others, the use of an efficient carrier for nucleic acid-based medicines is considered to be a determinant factor for the successful application of this promising therapeutic strategy. The drawbacks associated with the use of viral vectors, namely those related with safety problems, have prompted investigators to develop alternative methods for gene delivery, cationic lipid-based systems being the most representative. This review focuses on the various parameters that are considered to be crucial to optimize the use of cationic lipid-DNA complexes for gene therapy purposes. Particular emphasis is devoted to the analysis of the different stages involved in the transfection process, from the biophysical aspects underlying the formation of the complexes to the different biological barriers that need to be surpassed for gene expression to occur.

Animals↗
PubMed1998

Analysis and biophysical interpretation of bistable behaviour in thalamocortical neurons.

Thalamocortical neurons display a wide spectrum of activity patterns that are the expressions of the non-linear interactions between the various voltage-gated ion channels. Here, we show how bistable behaviour can emerge in these neurons, and how it is brought about by the steady-state residual ("window") component of IT, the low-threshold Ca2+ current. In particular, we present results that describe the dependence of bistability on two system parameters: the injected current and the leakage conductance. In addition, we provide a biophysical interpretation of these results by means of the properties of the electrical circuit representing the neuron membrane.

Algorithms↗
PubMed2003

Interpolating between Cellular Biophysics and Computation in Single Neurons.

What types of computations are performed on synaptic inputs within the dendritic trees of single neurons? In this issue of Neuron, present a systematic method to reduce complex, biophysically realistic neuron models to more tractable, simplified two-layered neural networks that could shed some light on this issue.

Biophysical Phenomena↗
PubMed1997

Potential of microsensor-based feedback bioactuators for biophysical cancer treatment.

Solid tumors usually exhibit a poorly organized vascularization and a deviant energy metabolism which result in an acidic pH and large hypoxic areas in the tumor microenvironment. A lot of cell biological data support the hypothesis that such physico-chemical conditions are promoters of the microevolution of malignant cells, inhibitors of the immune response, and co-factors for tumor cell invasion. Our experimental in vitro analyses and computer simulations indicate that the efficiency of immunotherapies and classical methods for cancer treatment might be improved if a physico-chemical microenvironment could be restored which reflects that found in normal tissue. In order to monitor and manipulate the tumor microenvironment, we suggest utilizing silicon-based feedback bioactuators which are controlled by on-line microsensors. These miniaturized bioactuators play the role of 'pH clamps' and can be implanted directly at the sites of inoperable tumors and metastases where they can reconstitute normal physico-chemical conditions. The drug application scheme can be precisely controlled by an integrated microprocessor. The paper summarizes the current state of development of such microsensor-based feedback bioactuators and outlines their potential for biophysical cancer treatment.

Adaptation, Physiological↗
PubMed1998

Biophysical compensation mechanisms buffering E. coli protein-nucleic acid interactions against changing environments.

Escherichia coli adapts to changes in growth osmolarity of at least 100-fold by making large changes in the amounts of intracellular water and solutes, including cytoplasmic K+. A wide range of in vitro salt, solute and biopolymer concentrations should therefore be considered 'physiological'. Paradoxically, these large, osmotically induced changes in cytoplasmic K+ concentration do not greatly affect the equilibria and kinetics of cytoplasmic protein-nucleic acid interactions. Biophysical effects resulting from changes in the amount of cytoplasmic water (such as macromolecular crowding) and in the concentrations of other cytoplasmic solutes appear to compensate for the effects of changes in cytoplasmic K+ concentration and thereby maintain protein-nucleic acid equilibria and kinetics in the range required for in vivo function.

Bacterial Proteins↗
PubMed1991

Biophysical processes in invertebrate photoreceptors: recent progress and a critical overview based on Limulus photoreceptors.

Limulus ventral nerve photoreceptor, a classical preparation for the study the phototransduction in invertebrate eyes, seems to have a very complex mechanism to transform light energy into a physiological signal. Although the main function of the photoreceptor is to change the membrane conductance according to the illumination, the cell has voltage-activated conductances as well. The voltage-gated conductances are matched to the light-activated ones in the sense that they make the function of the cell more efficient. The complex mechanism of phototransduction and the presence of four different voltage-gated conductance in Limulus ventral nerve photoreceptors indicate that these cells are far less differentiated than the photoreceptor cells of vertebrates. Indications accumulated in recent years support the view that the ventral photoreceptor of Limulus has different light-activated macroscopic current components, ion channels and terminal transmitters. After conclusions from macroscopic current measurements (Payne, 1986; Payne et al. 1986 a, b), direct evidence was presented by single-channel (Nagy & Stieve, 1990 a, b; Nagy, 1990 a, b) and macroscopic current measurements (Deckert et al. 1991 a, b) for three different light-activated conductances. It has been shown that two of these conductances are stimulated by two different excitation mechanisms. The two mechanisms, having different kinetics, release probably two different transmitters. One of them might be the cGMP (Johnson et al. 1986), the other one the calcium ion (Payne et al. 1986 a, b). However, the biochemical processes which link the rhodopsin molecules and the ion channels are not known. The unknown chemical details of the phototransduction result in a delay for the mathematical description of the biophysical mechanisms. More biochemical details are known about the adaptation mechanism. It was found that inositol 1,4,5-trisphosphate is a messenger for the release of calcium ions from the intracellular stores and that calcium ions are the messengers for adaptation (Payne et al. 1986 b; Payne & Fein, 1987). Concerning the mechanism of calcium release, it was revealed that a negative feedback acts on the enzyme cascade to regulate the internal calcium level and to protect the stores against complete emptying (Payne et al. 1988, 1990). Calcium ions also play an important role in the excitation mechanism. (a) In [Ca2+]i-depleted cells the light-induced current was increased after intracellular Ca2+ injection, suggesting that calcium is necessary for the transduction mechanism (Bolsover & Brown, 1985).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMedDate not supplied

Polyelectrolyte vectors for gene delivery: influence of cationic polymer on biophysical properties of complexes formed with DNA.

Cationic polymer/DNA complexes are widely used for gene delivery, although the influence of the cationic polymer on the biophysical properties of the resulting complex is poorly understood. Here, several series of cationic polymers have been used to evaluate the influence of structural parameters on properties of DNA complexes. Parameters studied included the length of side chain, charge type (primary versus tertiary and quaternary), polymer molecular weight, and charge spacing along the polymer backbone. Cationic polymers with short side chains (such as polyvinylamine) formed small complexes, resistant to destabilization by polyanions, with low surface charge, limited transfection activity, and efficient intranuclear transcription. Conversely, cationic polymers with long side chains (e.g., poly[methacryloyl-Gly-Gly-NH-(CH(2))(6)-NH(2))] showed inefficient complex formation, high positive surface charge, and better transfection activity. The effects of molecular weight varied between polymers, for example, low molecular weight poly(L-lysine) produced relatively small complexes, whereas low molecular weight poly[2-(trimethylammonio)ethyl methacrylate chloride] produced large aggregates. Polymers containing quaternary ammonium groups showed efficient complex formation but poor transfection. Finally, spreading charges widely on the polymer structure inhibited their ability to condense DNA. In summary, to achieve small, stable complexes, the use of cationic polymers with short side chains bearing primary amino groups is suggested.

Animals↗
PubMed1992

Biophysical characterization of a transit peptide directing chloroplast protein import.

We have investigated the biophysical properties of a 35 amino acid peptide representing the entire length of a chloroplastic targeting sequence. The peptide, termed gamma-tp, corresponds in sequence to the transit peptide of the gamma subunit of the chloroplast ATP synthase from Chlamydomonas reinhardtii. We found that gamma-tp blocks the import of the small subunit of ribulose-1,5-bisphosphate carboxylase/oxygenase into isolated pea chloroplasts (KI approximately 5 microM), suggesting that it interacts with higher plant plastids in a physiological manner. We also found the gamma-tp to have a high affinity for nonpolar environments, but not to cause a general disruption of membrane integrity. Hydrophobic moment analysis suggests that the gamma-tp can adopt an amphipathic beta structure. However, circular dichroism measurements indicate that the peptide is largely a random coil, in both the presence and absence of sodium laurylsulfate micelles. In the absence of a recognizable secondary structural targeting motif, we asked whether the presence of a transit peptide on a chloroplast protein increases the protein's overall affinity for nonpolar environments. Phase-partition experiments with Triton X-114 suggest that this is not the case. These results are discussed in relation to the mechanism of protein targeting to chloroplasts.

Algal Proteins↗
PubMed1994

Biophysical characterization of the c-Myb DNA-binding domain.

We have examined proteins containing the DNA-binding domain of c-Myb with biophysical methods. This DNA-binding domain consists of three imperfect repeats (R1, R2, and R3) conserved among many species. Our results indicate that the DNA-binding domain forms unspecific and specific complexes with oligodeoxynucleotides. In the presence of R1, DNA sequences related to a canonical c-Myb-binding site are better discriminated. Furthermore, although R2 and R3 are sufficient for sequence-specific DNA binding, a structural change of the DNA-binding domain upon specific complex formation is induced only when R1 is present. Therefore, R1 might serve as an important element required for secondary structure alteration upon binding and its stabilization as well as for better discrimination between specific and related DNA sequences.

Base Sequence↗
PubMed2002

Biophysical properties of camelid V(HH) domains compared to those of human V(H)3 domains.

Camelidae possess an unusual form of antibodies lacking the light chains. The variable domain of these heavy chain antibodies (V(HH)) is not paired, while the V(H) domain of all other antibodies forms a heterodimer with the variable domain of the light chain (V(L)), held together by a hydrophobic interface. Here, we analyzed the biophysical properties of four camelid V(HH) fragments (H14, AMD9, RN05, and CA05) and two human consensus V(H)3 domains with different CDR3 loops to gain insight into factors determining stability and aggregation of immunoglobulin domains. We show by denaturant-induced unfolding equilibria that the free energies of unfolding of V(HH) fragments are characterized by Delta G(N-U) values between 21.1 and 35.0 kJ/mol and thus lie in the upper range of values for V(H) fragments from murine and human antibodies. Nevertheless, the V(HH) fragments studied here did not reach the high values between 39.7 and 52.7 kJ/mol of the human consensus V(H)3 domains with which they share the highest degree of sequence similarity. Temperature-induced unfolding of the V(HH) fragments that were studied proved to be reversible, and the binding affinity after cooling was fully retained. The melting temperatures were determined to be between 60.1 and 66.7 degrees C. In contrast, the studied V(H)3 domains aggregated during temperature-induced denaturation at 63-65 degrees C. In summary, the camelid V(HH) fragments are characterized by a favorable but not unusually high stability. Their hallmark is the ability to reversibly melt without aggregation, probably mediated by the surface mutations characterizing the V(HH) domains, which allow them to regain binding activity after heat renaturation.

Amino Acid Sequence↗
PubMed2006

Probing hot spots at protein-ligand binding sites: a fragment-based approach using biophysical methods.

Mapping interactions at protein-ligand binding sites is an important aspect of understanding many biological reactions and a key part of drug design. In this paper, we have used a fragment-based approach to probe "hot spots" at the cofactor-binding site of a model dehydrogenase, Escherichia coli ketopantoate reductase. Our strategy involved the breaking down of NADPH (Kd = 300 nM) into smaller fragments and the biophysical characterization of their binding using WaterLOGSY NMR spectroscopy, isothermal titration calorimetry (ITC), and inhibition studies. The weak binding affinities of fragments were measured by direct ITC titrations under low c value conditions. The 2'-phosphate and the reduced nicotinamide groups were found to contribute a large part of the binding energy. A combination of ITC and site-directed mutagenesis enabled us to locate the fragments at separate hot spots on opposite ends of the cofactor-binding site. This study has identified structural determinants for cofactor recognition that represent a blueprint for future inhibitor design.

Alcohol Oxidoreductases↗
PubMed2004

Complexes of poly(ethylene glycol)-based cationic random copolymer and calf thymus DNA: a complete biophysical characterization.

Complete biophysical characterization of complexes (polyplexes) of cationic polymers and DNA is needed to understand the mechanism underlying nonviral therapeutic gene transfer. In this article, we propose a new series of synthesized random cationic polymers (RCPs) from methoxy poly(ethylene glycol) monomethacrylate (MePEGMA) and (3-(methacryloylamino)propyl)trimethylammonium chloride with different mole ratios (32:68, 11:89, and 6:94) which could be used as a model system to address and answer the basic questions relating to the mechanism of the interaction of calf thymus DNA (CT-DNA) and cationic polymers. The solubility of the complexes of CT-DNA and RCP was followed by turbidity measurements. It has been observed that complexes of RCP with 68 mol % MePEGMA precipitate near the charge neutralization point, whereas complexes of the other two polymers are water-soluble and stable at all compositions. Dnase 1 digestion experiments show that DNA is inaccessible when it forms complexes with RCP. Ethidium bromide exclusion and gel electrophoretic mobility show that both polymers are capable of binding with CT-DNA. Atomic force microscopy images in conjunction with light scattering experiments showed that the complexes are spherical in nature and 75-100 nm in diameter. Circular dichroism spectroscopy studies indicated that the secondary structure of DNA in the complexes is not perturbed due to the presence of poly(ethylene glycol) segments in the polymer. Furthermore, we used a combination of spectroscopic and calorimetric techniques to determine complete thermodynamic profiles accompanying the helix-coil transition of CT-DNA in the complexes. UV and differential scanning calorimetry melting experiments revealed that DNA in the complexes is more stable than in the free state and the extent of stability depends on the polymer composition. Isothermal titration calorimetry experiments showed that the binding of these RCPs to CT-DNA is associated with small exothermic enthalpy changes. A complete thermodynamic profile showed that the RCP/DNA complex formation is entropically favorable. Much broader opportunities to vary the architecture of the polymers studied here make these systems promising in addressing various basic and practical problems in gene delivery systems.

Animals↗
PubMed2001

Cyanide-induced alterations to the biophysical conformations of the isolated fish liver.

The purpose of this study is to examine the applicability of an infared spectroscopic methodology for the study of an environmental problem. The effect of cyanide concentrations on the biophysical conformation of the fish liver homogenate was determined by using an attenuated total reflectance (ATR)/Fourier transform infrared (FT-IR) microspectroscopy. Alive male model fish, Tilapia Zillii, was used. The liver from fish was isolated and homogenized in pH 8.0 Tris buffer solution. The results indicate that the IR peak intensity increased markedly in the C-H stretching range (3000-2800 cm-1), ester C = O stretching of lipids (1743 cm-1) and carbohydrate bands (1195-950 cm-1), but decreased in the amide I at 1649 cm-1 and the free asymmetric stretching band of phosphate at 1261 cm-1 with the increase of KCN concentrations. The marked release of hepatic enzymes and glutathione into homogenate induced by cyanide might account for the higher IR spectral peak intensity of fish liver tissue after treatment with KCN. The cyanide was also found to induce the protein structure of fish liver homogenate from alpha-helical conformation to beta-conformation.

Animals↗