Signal propagation in stem-cell niches

Stem cells, maintaining tissue homeostasis, are nurtured in microscopic niches formed of so-called environmental cells. The kinetics of proliferation and differentiation of stem cells in such niches depend on their interaction with the messenger proteins secreted by environmental cells. We propose a generic mean-field kinetic model of the propagation of such signals. To motivate our study, we briefly describe a stem-cell niche in the Drosophila ovary. Our model is however applicable to other niches as well. In particular, it helps one to understand the necessary conditions for the niche function. For example, the model predicts that in the case of the Drosophila ovary each germline stem cell should have in the external membrane at least 700 receptors interacting with the signaling Dpp and Gpp proteins emanating from the cap cells.     

Statistical characteristics of photon distributions in a semi-infinite turbid medium: Analytical expressions and their application to optical tomography

The paper focuses on the determination of statistical characteristics of photon distributions in a semi-infinite turbid medium, specifically the photon average trajectory and the root-mean-square deviation of photons from the average trajectory, with an approach based on the diffusion approximation to the radiative transfer equation. We show that the Dirichlet and Robin boundary conditions used for this purpose give close results. We derive exact analytical expressions for the case of the Dirichlet boundary condition. To demonstrate the practical value of our results we consider approximate solution of the inverse problem of time-domain diffuse optical tomography with the flat layer transmission geometry. The problem is solved with the method of photon average trajectories which are constructed with analytical expressions derived for a semi-infinite medium.     

Study on the preparation of chitosan-alginate complex membrane and the effects on adhesion and activation of endothelial cells

Biomaterials that support vascularization without activating immune competent endothelial cells are desirous in immunoisolation. The aim of the present study was to evaluate effect of chitosan-alginate membrane on adhesion and activation of endothelial cells. The AFM photographs showed that the CS/ALG membrane surface roughness values were less than CS membrane and ALG membrane. The contact angle of CS/ALG membrane was between ALG membrane and CS membrane. The surface roughness and hydrophilicity of CS/ALG membrane affect the adhesion and activation on endothelial cells. The CS/ALG membrane did not allow the majority of cells to adhere well but maintained their viability. The membrane leach-outs were nontoxic to the cells, as confirmed by tetrazolium reduction (MTT) and trypan blue assays. The growth curves of the endothelial cells desquamated from the CS/ALG membrane suggested that the endothelial cells maintain their activation. Taken together these results point out that CS/ALG membrane is compatible with endothelial cells and maintains their nonactivated status.     

Elastic Interaction between a String of Cells and an Individual Cell

The elastic interaction between a string of cells and an individual cell on an elastic substrate is investigated numerically using the force-dipole model. This interaction is found to be of short range, and the cut-off distance is about 1.4 times of the length of the cell. The energy-minimization distance is about half the cellular length. The specific relationship between the cellular reorientation and the cellular position are obtained quantitatively. A critical distance is found, and the cellular orientation has an abrupt change at this transition point.     

Entropy of electromyography time series

A nonlinear analysis based on Renyi entropy is applied to electromyography (EMG) time series from back muscles. The time dependence of the entropy of the EMG signal exhibits a crossover from a subdiffusive regime at short times to a plateau at longer times. We argue that this behavior characterizes complex biological systems. The plateau value of the entropy can be used to differentiate between healthy and low back pain individuals.     

Parameter selection in a Peyrard-Bishop-Dauxois model for DNA dynamics

In this Letter we study possible intervals for some parameters existing in the Peyrard-Bishop-Dauxois (PBD) model for the DNA dynamics. These parameters describe longitudinal and helicoidal interactions between nucleotides and a Morse potential approximating transverse interactions. We also estimate a possible interval for a wave number of a carrier component of a modulated solitonic wave. Finally, we compare our statements with experimental value of solitonic velocity in DNA.     

Translocation of Biopolymer Chain Through a Nanopore: Coil--Helix Transition

The translocation dynamics of a single biopolymer chain through a nanopore in a membrane is investigated by taking the coil-helix transition into account. Based on the changing of the free energy due to the coil-helix transition, the mean first passage time T is obtained, and then the corresponding numerical simulations are presented under different conditions. It is shown that the coil--helix transition can significantly shorten the translocation time of the biopolymer chain. In addition, we also discuss the scaling behaviour for T with the chain length N and some related problems.     

Co-Adsorption of CO in NO-CO Reaction on a Metal Catalytic Surface Studied by Computer Simulation

The effect of co-adsorption of CO molecules in the NO-CO reaction on a metal catalytic surface like Pt（001） is studied by applying the Langmuir-Hinshelwood mechanism using the Monte Carlo simulations. The system is investigated by two approaches of NO adsorption; dissociatively at two empty surface sites and molecularly at a single vacant site. The elementary steps are the same as those in the conventional Ziff-Gulari-Barshad model. With the additional reaction step of co-adsorption, the sustained production of CO2 is obtained, which has never been seen on a square lattice without introducing additional parameters. The most interesting result is the elimination of continuous second order phase transition, i.e. the production of CO2 starts as soon as the partial pressure of CO departs from zero, which is in accordance with the experimental observations. The effect of co-adsorption probability on the phase diagrams has also been studied.     

Folding kinetics of two-state proteins based on the model of general random walk in native contact number space

We investigated the folding kinetics of a series of two-state proteins by using the model of general random walk in native contact number space, and derive the observed linear relationship between the logarithms of the folding rate constants and the numbers of native contacts from “kinetic viewpoint”. The protein folding speed limit and stability in this model are consistent with experimental observations.     

Simulation study of lateral diffusion in lipid-sterol bilayer mixtures

We employ off-lattice Monte Carlo simulations to study lateral diffusion in lipid-sterol bilayers using a two-dimensional model system which has been designed to simulate the experimental phase diagrams of both lipid-cholesterol and lipid-lanosterol systems. We focus on the effects of varying sterol concentration and temperature on the tracer diffusion coefficient, D, which characterizes the lateral motion of single tagged lipids in a bilayer. Generally, we find that increasing the cholesterol concentration suppresses D due to an increased conformational ordering of lipid chains. We argue that this effect competes with an increase in the average free area per lipid, which favours an increase in D. At temperatures close to the main transition temperature, the competition between the two effects leads to intriguing behavior of D. Overall, the model results are in excellent qualitative agreement with available experimental results for lipid-cholesterol mixtures. Additional studies of a model lipid-lanosterol system, for which experimental diffusion results are not available, predict that the presence of lanosterol has a smaller effect than cholesterol on reducing D relative to the pure lipid system. We conclude that the molecular model employed contains the essential features required to describe many of the qualitative features of the lateral diffusion behavior in lipid-sterol systems. Received 24 November 2000 and Received in final form 30 April 2001     

Strategies for the separation of polyelectrolytes based on non-linear dynamics and entropic ratchets in a simple microfluidic device

We perform Monte Carlo simulations of an existing electrophoretic microchannel device used for the size separation of large DNA fragments. This device is normally operated with a constant (dc) driving field. In contrast, we consider the case of a varying (ac) driving field, in the zero-frequency limit. We find that a time-asymmetric pulse can yield interesting migration regimes, in particular bidirectional transport for different molecular sizes. We also study a spatially asymmetric version of the device and show that it can rectify unbiased but non-equilibrium molecular motion, in agreement with previous predictions for entropic ratchets. Finally, at finite frequency we uncover a resonance for the molecular velocity in the channel which could lead to improved performance. Received: 16 November 2001 / Accepted: 11 February 2002 / Published online: 22 April 2002     

Molecular Dynamics Simulation of Myoglobin Collision with Low Energy Ions

Collisions of a low energy heavy ion with a myoglobin in water are simulated by molecular dynamics model. The increase of total energy is very small. The mean squared fluctuation decreases at 300 K and increases at 250K. This is an important novel cooling effect that protects the protein from ion damage. The possible collision side effect is the change of tertiary structure that blocks the normal functions of the myoglobin.     

Folding/unfolding kinetics of lattice proteins studied using a simple statistical mechanical model for protein folding, I: Dependence on native structures and amino acid sequences

The folding/unfolding kinetics of a three-dimensional lattice protein was studied using a simple statistical mechanical model for protein folding that we developed earlier. We calculated a characteristic relaxation rate for the free energy profile starting from a completely unfolded structure (or native structure) that is assumed to be associated with a folding rate (or an unfolding rate). The chevron plot of these rates as a function of the inverse temperature was obtained for four lattice proteins, namely, proteins a1, a2, b1, and b2, in order to investigate the dependency of the folding and unfolding rates on their native structures and amino acid sequences. Proteins a1 and a2 fold to the same native conformation, but their amino acid sequences differ. The same is the case for proteins b1 and b2, but their native conformation is different from that of proteins a1 and a2. However, the chevron plots of proteins a1 and a2 are very similar to each other, and those of proteins b1 and b2 differ considerably. Since the contact orders of proteins b1 and b2 are identical, the differences in their kinetics should be attributed to the amino acid sequences and consequently to the interactions between the amino acid residues. A detailed analysis revealed that long-range interactions play an important role in causing the difference in the folding rates. The chevron plots for the four proteins exhibit a chevron rollover under both strongly folding and strongly unfolding conditions. The slower relaxation time on the broad and flat free energy surfaces of the unfolding conformations is considered to be the main origin of the chevron rollover, although the free energy surfaces have features that are rather complicated to be described in detail here. Finally, in order to concretely examine the relationship between changes in the free energy profiles and the chevron plots, we illustrate some examples of single amino acid substitutions that increase the folding rate.     

Molecular Dynamics Simulation on Charge Transfer Relaxation between Myoglobin and Water

Dynamical processes of myoglobin after photon-excited charge transfer between Fe ion and surrounding water anion are simulated by a molecular dynamics model. The roles of Coulomb interaction effect and water effect in the relaxation process are discussed. It is found that the relaxations before and after charge transfer are similar. Strong Coulomb interactions and less water mobility decrease Coulomb energy fluctuations. An extra transferred charge of Fe ion has impact on water packing with a distance up to 0.86nm.     

Active Control of Cellular Orientation through In-Situ Stress in the Substrate

We investigate the orientation of cells on substrates to find possible methods for controlling the cellular orientation. The force dipole model is employed in our modelling and simulation. The elastic interaction between cells as well as the elastic interaction between the cell and in-situ stress field in the substrate are found to be the two main physical mechanisms to control the cellular orientation. The former interaction dominates the cellular orientation when the in-situ stress is small, while the later dominates when the in-situ stress is large enough. Two cells tend to align perpendicularly on a free substrate, but the cellular orientation varies with the increasing in-situ stress. Two cells tendto align in parallel when the normal stress is large enough. Their direction is perpendicular to the extension stress direction or parallel to the compression stress direction. When the positive in-situ shear stress is large enough, the two cells tend to align at -45°. Based on this theoretical simulation, it is believed that the cellular orientation on substrates can be controlled by thein-situ stresses.     

Percolation in a network with long-range connections: Implications for cytoskeletal structure and function

Cell shape, signaling, and integrity depend on cytoskeletal organization. In this study we describe the cytoskeleton as a simple network of filamentary proteins (links) anchored by complex protein structures (nodes). The structure of this network is regulated by a distance-dependent probability of link formation as P=p/d^s, where p regulates the network density and s controls how fast the probability for link formation decays with node distance (d). It was previously shown that the regulation of the link lengths is crucial for the mechanical behavior of the cells. Here we examined the ability of the two-dimensional network to percolate (i.e. to have end-to-end connectivity), and found that the percolation threshold depends strongly on s. The system undergoes a transition around s=2. The percolation threshold of networks with s<2 decreases with increasing system size L, while the percolation threshold for networks with s>2 converges to a finite value. We speculate that s<2 may represent a condition in which cells can accommodate deformation while still preserving their mechanical integrity. Additionally, we measured the length distribution of F-actin filaments from publicly available images of a variety of cell types. In agreement with model predictions, cells originating from more deformable tissues show longer F-actin cytoskeletal filaments.     

Interaction between B-Doped C60 Fullerene and Glycine Amino Acid from First-Principles Simulation

The possibility of formation of complexes between glycine and boron doped C60 （C59B） fullerene is investigated and compared with that of C60 fullerene by using the density functional theory calculations. It has been found that the binding of glycine to C59B generated the most stable complexes via its carbonyl oxygen active site, with a binding energy of-37.89 kcal/mol, while the glycine molecule prefers to bind to the pure C60 cage via its amino nitrogen active site, consistent with the recent experimental and theoretical studies. We have also tested the stability of the most stable Gly-C59B complex with ab initio molecular dynamics simulation, carried out at room temperature. These indicate that the B-doped C60 fullerenes seem to be more suitable materials for bindings to proteins than pure C60 fullerenes.     

Structural class tendency of polypeptide: A new conception in predicting protein structural class

Prediction of protein domain structural classes is an important topic in protein science. In this paper, we proposed a new conception: structural class tendency of polypeptides (SCTP), which is based on the fact that a given amino acid fragment tends to be presented in certain type of proteins. The SCTP is obtained from an available training data set PDB40-B. When using the SCTP to predict protein structural classes by Intimate Sorting predictive method, we got the predictive accuracy (jackknife test) with 93.7%, 96.5%, and 78.6% for the testing data set PDB40-j, Chou&Maggiora and CHOU. These results indicate that the SCTP approach is quite encouraging and promising. This new conception provides an effective tool to extract valuable information from protein sequences.