Downhill kinetics of biomolecular interface binding: Globally connected scenario

We study the kinetics of the biomolecular binding process at the interface using energy landscape theory. The global kinetic connectivity case is considered for a downhill funneled energy landscape. By solving the kinetic master equation, the kinetic time for binding is obtained and shown to have a U-shape curve-dependence on the temperature. The kinetic minimum of the binding time monotonically decreases when the ratio of the underlying energy gap between native state and average non-native states versus the roughness or the fluctuations of the landscape increases. At intermediate temperatures,fluctuations measured by the higher moments of the binding time lead to non-Poissonian, non-exponential kinetics. At both high and very low temperatures, the kinetics is nearly Poissonian and exponential.

Dominant kinetic paths on biomolecular binding-folding energy landscape

The identification of kinetic pathways is a central issue in understanding the nature of flexible binding. A new approach is proposed here to study the dynamics of this binding-folding process through the establishment of a path integral framework on the underlying energy landscape. The dominant kinetic paths of binding and folding can be determined and quantified. In this case, the corresponding kinetic paths of binding are shown to be intimately correlated with those of folding and the dynamics becomes quite cooperative. The kinetic time can be obtained through the contributions from the dominant paths and has a U-shape dependence on temperature.

Effects of chain flexibility on polymer conformation in dilute solution studied by lattice Monte Carlo simulation

Effects of chain flexibility on the conformation of homopolymers in good solvents have been investigated by Monte Carlo simulation. Bond angle constraint coupled with persistence length of polymer chains has been introduced in the modified eight-site bond fluctuation simulation model. The study about the effects of chain flexibility on polymer sizes reveals that the orientation of polymer chains under confinement is driven by the loss of conformation entropy. The conformation of polymer chains undergoing a gradual change from spherical iso-diametric ellipsoid to rodlike iso-diametric ellipsoid with the decrease of polymer chain flexibility in a wide region has been clearly illustrated from several aspects. Furthermore, a comparison of the freely jointed chain (FJC) model and the wormlike chain (WLC) model has also been made to describe the polymer sizes in terms of chain flexibility and quasi-quantitative boundary toward the suitability of the models.

First-passage time distribution and non-Markovian diffusion dynamics of protein folding

We study the kinetics of protein folding via statistical energy landscape theory. We concentrate on the local-connectivity case, where the configurational changes can only occur among neighboring states, with the folding progress described in terms of an order parameter given by the fraction of native conformations. The non-Markovian diffusion dynamics is analyzed in detail and an expression for the mean first-passage time (MFPT) from non-native unfolded states to native folded state is obtained. It was found that the MFPT has a V-shaped dependence on the temperature. We also find that the MFPT is shortened as one increases the gap between the energy of the native and average non-native folded states relative to the fluctuations of the energy landscape. The second- and higher-order moments are studied to infer the first-passage time distribution. At high temperature, the distribution becomes close to a Poisson distribution, while at low temperatures the distribution becomes a Levy-type distribution with power-law tails, indicating a nonself-averaging intermittent behavior of folding dynamics. We note the likely relevance of this result to single-molecule dynamics experiments, where a power law (Levy) distribution of the relaxation time of the underlined protein energy landscape is observed.

In situ electrochemical scanning tunnelling microscopy investigation of structure for horseradish peroxidase and its electrocatalytic property

Immobilization of protein molecules is a fundamental problem for scanning tunnelling microscopy (STM) measurements with high resolution. In this paper, an electrochemical method has been proved to be an effective way to fix native horseradish peroxidase (HRP) as well as inactivated HRP from electrolyte onto a highly oriented pyrolytic graphite (HOPG) surface. This preparation is suitable for both ex situ and in situ electrochemical STM (ECSTM) measurements. In situ STM has been successfully employed to observe totally different structures of HRP in three typical cases: (1) in situ ECSTM reveals an oval-shaped pattern for a single molecule in neutral buffer solution, which is in good agreement with the dimension determined as 6.2 x 4.3 x 1.2. nm(3) by ex situ STM for native HRP; (2) in situ ECSTM shows that the adsorbed HRP molecules on HOPG in a denatured environment exhibit swelling globes at the beginning and then change into a V-shaped pattern after 30 min; (3) in situ ECSTM reveals a black hole in every ellipsoidal sphere for inactivated HRP in strong alkali solution. The cyclic voltammetry results indicate that the adsorbed native HRP can directly catalyse the reduction of hydrogen peroxide, demonstrating that a direct electron transfer reduction occurred between the enzyme and HOPG electrode, whereas the corresponding cyclic voltammograms for denatured HRP and inactivated HRP adsorbed on HOPG electrodes indicate a lack of ability to catalyse H2O2 reduction, which confirms that the HRP molecules lost their biological activity. Obviously, electrochemical results powerfully support in situ STM observations.

Sensitivity map of laser tweezers Raman spectroscopy for single-cell analysis of colorectal cancer

Raman spectroscopy on single, living epithelial cells captured in a laser trap is shown to have diagnostic power over colorectal cancer. This new single-cell technology comprises three major components: primary culture processing of human tissue samples to produce single-cell suspensions, Raman detection on singly trapped cells, and diagnoses of the cells by artificial neural network classifications. it is compared with DNA flow cytometry for similarities and differences. Its advantages over tissue Raman spectroscopy are also discussed. In the actual construction of a diagnostic model for colorectal cancer, real patient data were taken to generate a training set of 320 Raman spectra and, a test set of 80. By incorporating outlier corrections to a conventional binary neural classifier, our network accomplished significantly better predictions than logistic regressions, with sensitivity improved from 77.5% to 86.3% and specificity improved from 81.3% to 86.3% for the training set and moderate improvements for the test set. Most important, the network approach enables a sensitivity map analysis to quantitate the relevance of each Raman band to the normal-to-cancer transform at the cell level. Our technique has direct clinic applications for diagnosing cancers and basic science potential in the study of cell dynamics of carcinogenesis. (C) 2007 Society of Photo-Optical Instrumentation Engineers.

Study of the effect of alcohol on single human red blood cells using near-infrared laser tweezers Raman spectroscopy

The effect of alcohol solution on single human red blood Cells (RBCs) was investigated using near-infrared laser tweezers Raman spectroscopy (LTRS). In our system, a low-power diode laser at 785 nm was applied for the trapping of a living cell and the excitation of its Raman spectrum. Such a design could simultaneously reduce the photo-damage to the cell and suppress the interference from the fluorescence on the Raman signal. The denaturation process of single RBCs in 20% alcohol solution was investigated by detecting the time evolution of the Raman spectra at the single-cell level. The vitality of RBCs was characterized by the Raman band at 752 cm(-1), which corresponds to the porphyrin breathing mode. We found that the intensity of this band decreased by 34.1% over a period of 25 min after the administration of alcohol. In a further study of the dependence of denaturation on alcohol concentration, we discovered that the decrease in the intensity of the 752 cm(-1) band became more rapid and more prominent as the alcohol concentration increased. The present LTRS technique may have several potential applications in cell biology and medicine, including probing dynamic cellular processes at the single cell level and diagnosing cell disorders in real time. Copyright (c) 2005 John Wiley T Sons, Ltd.

Diagnosis of colorectal cancer using Raman spectroscopy of laser-trapped single living epithelial cells

A single-cell diagnostic technique for epithelial cancers is developed by utilizing laser trapping and Raman spectroscopy to differentiate cancerous and normal epithelial cells. Single-cell suspensions were prepared from surgically removed human colorectal tissues following standard primary culture protocols and examined in a near-infrared laser-trapping Raman spectroscopy system, where living epithelial cells were investigated one by one. A diagnostic model was built on the spectral data obtained from 8 patients and validated by the data from 2 new patients. Our technique has potential applications from epithelial cancer diagnosis to the study of cell dynamics of carcinogenesis. (c) 2006 Optical Society of America.

Sensitivity map of laser tweezers Raman spectroscopy for single-cell analysis of colorectal cancer

Raman spectroscopy on single, living epithelial cells captured in a laser trap is shown to have diagnostic power over colorectal cancer. This new single-cell technology comprises three major components: primary culture processing of human tissue samples to produce single-cell suspensions, Raman detection on singly trapped cells, and diagnoses of the cells by artificial neural network classifications. it is compared with DNA flow cytometry for similarities and differences. Its advantages over tissue Raman spectroscopy are also discussed. In the actual construction of a diagnostic model for colorectal cancer, real patient data were taken to generate a training set of 320 Raman spectra and, a test set of 80. By incorporating outlier corrections to a conventional binary neural classifier, our network accomplished significantly better predictions than logistic regressions, with sensitivity improved from 77.5% to 86.3% and specificity improved from 81.3% to 86.3% for the training set and moderate improvements for the test set. Most important, the network approach enables a sensitivity map analysis to quantitate the relevance of each Raman band to the normal-to-cancer transform at the cell level. Our technique has direct clinic applications for diagnosing cancers and basic science potential in the study of cell dynamics of carcinogenesis. (C) 2007 Society of Photo-Optical Instrumentation Engineers.

Optical spectroscopy of Yb3Al5O12 single crystal

Yb3Al5O12 single crystal has been grown by Czochralski (CZ) method. The absorption spectrum was investigated at low temperature and the electronic energy levels for F-2(5/2) multiplet of Yb3+ in YbAG was proposed. The up-conversion emission of the crystal under 940 nm diode pumping and the X-ray excited luminescence (XEL) features of the crystal were also studied. (c) 2005 Elsevier B.V. All rights reserved.

Surface-enhanced resonant Raman spectroscopy (SERRS) of single-walled carbon nanotubes absorbed on the Ag-coated anodic aluminum oxide (AAO) surface

In this paper, we developed a new kind of substrate, the silver-coated anodic aluminum oxide (AAO), to investigate the characters of surface-enhanced resonant Raman scattering (SERRS) of the dilute single-walled carbon nanotubes. Homogeneous Ag-coated AAO substrate was obtained by decomposing the AgNO3 on the surface of AAO. single-walled carbon nanotubes (SWNTs) were directly grown onto this substrate through floating catalyst chemical vapor deposition method (CVD). SERRS of SWNTs was carried out using several different wavelength lasers. The bands coming from metallic SWNTs were significantly enhanced. The two SERRS mechanisms, the "electromagnetic" and "chemical" mechanism, were mainly responsible for the experiment results. (c) 2005 Elsevier B.V. All rights reserved.

Interface-related in-plane optical anisotropy in GaAs/AlxGa1-xAs single-quantum-well structures studied by reflectance difference spectroscopy

The in-plane optical anisotropies of a series of GaAs/AlxGa1-xAs single-quantum-well structures have been observed at room temperature by reflectance difference spectroscopy. The measured degree of polarization of the excitonic transitions is inversely proportional to the well width. Numerical calculations based on the envelope function approximation incorporating the effect of C-2v-interface symmetry have been performed to analyze the origin of the optical anisotropy. Good agreement with the experimental data is obtained when the optical anisotropy is attributed to anisotropic-interface structures. The fitted interface potential parameters are consistent with predicted values.

In-plane optical anisotropy in GaAsN/GaAs single-quantum well investigated by reflectance-difference spectroscopy

The interface properties of GaNxAs1-x/GaAs single-quantum well is investigated at 80 K by reflectance difference spectroscopy. Strong in-plane optical anisotropies (IPOA) are observed. Numerical calculations based on a 4 band K . P Hamiltonian are performed to analyze the origin of the optical anisotropy. It is found that the IPOA can be mainly attributed to anisotropic strain effect, which increases with the concentration of nitrogen. The origin of the strain component epsilon(xy) is also discussed.