Mechano-Chemical Coupling at Molecular Level: Forced Dissociation of Selectin/Ligand Binding

Mechano-chemical coupling is a common phenomenon that exists in various biological processes at different physiological levels. Bone tissue remodeling strongly depends on the local mechanical load. Leukocytes are sheared to form the transient aggregates with platelets or other leukocytes in the circulation. Flow pattern affects the signal transduction pathways in endothelial cells. Receptor/ligand interactions are important to cell adhesion since they supply the physical linkages...

Forced Dissociation of Selectin-ligand Complexes Using Steered Molecular Dynamics Simulation

Selectin-ligand interactions are crucial to such biological processes as inflammatory cascade or tumor metastasis. How transient formation and dissociation of selectin-ligand bonds in blood flow are coupled to molecular conformation at atomic level, however, has not been well understood. In this study, steered molecular dynamics (SMD) simulations were used to elucidate the intramolecular and intermolecular conformational evolutions involved in forced dissociation of three selectin-ligand systems: the construct consisting of P-selectin lectin (Lec) and epidermal growth factor (EGF)-like domains (P-LE) interacting with synthesized sulfoglycopeptide or SGP-3, P-LE with sialyl Lewis X (sLeX), and E-LE with sLeX. SMD simulations were based on newly built-up force field parameters including carbohydrate units and sulfated tyrosine(s) using an analogy approach. The simulations demonstrated that the complex dissociation was coupled to the molecular extension. While the intramolecular unraveling in P-LESGP-3 system mainly resulted from the destroy of the two anti-parallel sheets of EGF domain and the breakage of hydrogen-bond cluster at the Lec-EGF interface, the intermolecular dissociation was mainly determined by separation of fucose (FUC) from Ca2+ ion in all three systems. Conformational changes during forced dissociations depended on pulling velocities and forces, as well as on how the force was applied. This work provides an insight into better understanding of conformational changes and adhesive functionality of selectin-ligand interactions under external forces.

Influence of Forced Convection on Columnar Microstructure During Directional Solidification of Al-Ni Alloys

This paper presents a summary of cellular and dendritic morphologies resulting from the upward directional solidification of Al - Ni alloys in a cylindrical crucible. We analysed the coupling of solid-liquid interface morphology with natural and forced convection. The influence of natural convection was first analyzed as a function of growth parameters (solute concentration, growth rate and thermal gradient). In a second step, the influence of axial vibrations on solidification microstructure was investigated by varying vibration parameters (amplitude and frequency). Experimental results were compared to preliminary numerical simulations and a good agreement is found for natural convection. In this study, the critical role of the mushy zone in the interaction between fluid flow and solidification microstructure is pointed out.

Forced extension of P-selectin construct using steered molecular dynamics

P-selectin, a 70-nm-long cellular adhesive molecule, possesses elastic and extensible properties when neutrophils roll over the activated endotheliam of blood vessel in inflammatory reaction. Transient formation and dissociation of P-selectin/ligand bond on applied force of blood flow induces the extension of P-selectin and relevant ligands. Steered molecular dynamics simulations were performed to stretch a single P-selectin construct consisting of a lectin (Lec) domain and an epithelial growth factor (EGF)-like domain, where P-selectin construct was forced to extend in water with pulling velocities of 0.005-0.05 nm/ps and with constant forces of 1000-2500 pN respectively. Resulting force-extension profiles exhibited a dual-peak pattern on various velocities, while both plateaus and shoulders appeared in the extension-time profiles on various forces. The force or extension profiles along stretching pathways were correlated to the conformational changes, suggesting that the structural collapses of P-selectin Lec/EGF domains were mainly attributed to the burst of hydrogen bonds within the major beta sheet of EGF domain and the disruptions of two hydrophobic cores of Lee domain. This work furthers the understanding of forced dissociation of P-selectin/ligand bond.

Low Spring Constant Regulates P-Selectin-Psgl-1 Bond Rupture

Forced dissociation of selectin-ligand bonds is crucial to such biological processes as leukocyte recruitment, thrombosis formation, and tumor metastasis. Although the bond rupture has been well known at high loading rate r(f) (>= 10(2) pN/s), defined as the product of spring constant k and retract velocity v, how the low r(f) (< 10(2) pN/s) or the low k regulates the bond dissociation remains unclear. Here an optical trap assay was used to quantify the bond rupture at r(f) <= 20 pN/s with low k (similar to 10(-3)-10(-2) pN/nm) when P-selectin and P-selectin glycoprotein ligand 1 (PSGL-1) were respectively coupled onto two glass microbeads. Our data indicated that the bond rupture force f retained the similar values when r(f) increased up to 20 pN/s. It was also found that f varied with different combinations of k and v even at the same r(f). The most probable force, f

Instability of the vertically forced surface wave in a circular cylindrical container

The nonlinear amplitude equation, which was derived by Jian Yongjun employing expansion of two-time scales in inviscid fluids in a vertically oscillating circular cylindrical vessel, is modified by introducing a damping term due to the viscous dissipation of this system. Instability of the surface wave is analysed and properties of the solutions of the modified equation are determined together with phase-plane trajectories. A necessary condition of forming a stable surface wave is obtained and unstable regions are illustrated. Research results show that the stable pattern of surface wave will not lose its stability to an infinitesimal disturbance.

Vertically forced surface wave in weakly viscous fluids bounded in a circular cylindrical vessel

Two-time scale perturbation expansions were developed in weakly viscous fluids to investigate surface wave motions by linearizing the Navier-Stokes equation in a circular cylindrical vessel which is subject to a vertical oscillation. The fluid field was divided into an outer potential flow region and an inner boundary layer region. A linear amplitude equation of slowly varying complex amplitude, which incorporates a damping term and external excitation, was derived for the weakly viscid fluids. The condition for the appearance of stable surface waves was obtained and the critical curve was determined. In addition, an analytical expression for the damping coefficient was determined and the relationship between damping and other related parameters (such as viscosity, forced amplitude, forced frequency and the depth of fluid, etc.) was presented. Finally, the influence both of the surface tension and the weak viscosity on the mode formation was described by comparing theoretical and experimental results. The results show that when the forcing frequency is low, the viscosity of the fluid is prominent for the mode selection. However, when the forcing frequency is high, the surface tension of the fluid is prominent.

Internal resonance of an L-shaped beam with a limit stop .2. Forced vibration

A limit stop is placed at the elbow of an L-shaped beam whose linear natural frequencies are nearly commensurable. As a result of this hardening device the non-linear system exhibits multiple internal resonances, which involve various degree of coupling between the first five modes of the beam in free vibration. A point load is so placed as to excite several modes and the resulting forced vibration is examined. In the undamped case, three in-phase and two out-of-phase solution branches have been found. The resonance curve is extremely complicated, with multiple branches and interactions between the first four modes. The amplitudes of the higher harmonics are highly influenced by damping, the presence of which can effectively attenuate internal resonances. Consequently parts of the resonance curve may be eliminated, with the resulting response comprising different distinctive branches. (C) 1996 Academic Press Limited

2D Kinetics and Forced Dissociation of Selectin-ligand Bindings

Cell adhesion is crucial to many pathophysiological processes, such as inflammatory reaction and tumor metastasis. It is mediated by specific interactions between receptors and ligands, and provides the physical linkages among cells. For example, interactions between selectins and glycoconjugate ligands mediate leukocyte initially tethering to and subsequently rolling on vascular surfaces in sites of inflammation or injury, which is determined by their fast kinetic rates. To mediate cell adhesion, the interacting receptors and ligands must anchor to apposing surfaces of two cells or a cell and the substratum, i.e. , the so-called two-dimensional (2D) binding, which differs from interactions in the fluid phase, i.e. , the three-dimensional (3D) binding. How structural variations and surface environments of interacting molecules affect their 2D kinetics, and how external forces manipulate their dissociation has little been known quantitatively, and nowadays attracts more and more attentions.

Experimental investigation on TBAB clathrate hydrate slurry flows in a horizontal tube: Forced convective heat transfer behaviors

Tetra-n-butyl-ammonium bromide (TBAB) clathrate hydrate slurry (CHS) is one kind of secondary refrigerants, which is promising to be applied into air-conditioning or latent-heat transportation systems as a thermal storage or cold carrying medium for energy saving. It is a solid-liquid two phase mixture which is easy to produce and has high latent heat and good fluidity. In this paper, the heat transfer characteristics of TBAB slurry were investigated in a horizontal stainless steel tube under different solid mass fractions and flow velocities with constant heat flux. One velocity region of weakened heat transfer was found. Moreover, TBAB CHS was treated as a kind of Bingham fluids, and the influences of the solid particles, flow velocity and types of flow on the forced convective heat transfer coefficients of TBAB CHS were investigated. At last, criterial correlations of Nusselt number for laminar and turbulent flows in the form of power function were summarized, and the error with experimental results was within 20%.

Measurement of respiratory acoustic impedance in children by a modified forced oscillation method

An introduction to a modified forced oscillation method, square-wave excitation technique, including fundamentals and methods, as used in respiratory function examination. On the basis of experimental results and theoretical predictions, we suggest that Respiratory Acoustic Impedance (RAI) measurement by spectral analysis can significantly improve estimation of contribution to RAI from different part of respiratory tract. The outcome is of considerable interest in the study of lung disease, such as COPD and asthma in young children.

Effects of forced solution flow on lysozyme crystal growth

In order to study quantitatively the effects of forced solution on crystal growth, we designed a new set of experimental equipment, in particular, a microchannel mixer was used as crystallization container so that the consumption of protein samples was much reduced and thus an exact syringe pump could be used for precise control of the flow rates. Since the mixer’s section was designed to be rectangular, the solution velocity in its center was steady and constant, and thus repeatable experiments were facilitated. Experimental results showed that the effects of forced solution on protein crystal growth were different under different levels of supersaturation, and new results were obtained for cases of high supersaturation. When the supersaturation is σ = 2.3, with increasing flow rates the growth rates of the lysozyme crystal’s (110) face hardly change when the flow rates are lower than 1300 μm/s, and decrease quickly afterwards. When the flow rate reaches 2000 μm/s, the crystal nearly ceases to grow. When the supersaturation is σ = 2.7, with increasing flow rates the (110) face growth rates increase at the beginning then reach the maximum values at 1700 μm/s – 1900 μm/s and decrease afterwards, approaching zero or so when the flow rate reaches 12000 μm/s. The higher the supersaturation, the larger the flow rate at which the crystal ceases to grow. © 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

Conducting polyaniline film from aqueous dispersion: Crystallizable side chain forced lamellar structure for high conductivity

Aqueous conducting polyaniline dispersion was prepared employing acidic phosphate ester bearing hydrophilic ethylene glycol segment as dopant, and conducting film with electrical conductivity of 25 S/cm was obtained from the dispersion. Ordered self-assembly lamellar structure with interlamellar distance of 1.2 nm was observed in the film, which consisted of alternating layers of rigid polyaniline chain and flexible phosphate ester side chains, where the phosphate side chain layer was separated by two rigid polyaniline layers. The lamellar structure leading to high conducting film was formed due to the confinement of polyaniline chain by crystallizable phosphate side chain, since the electrical conductivity decreased by four orders of magnitude once the dopant side chain crystalline was destroyed. The crystallizable side chain forced lamellar structure is expected to be a new chance for highly conducting polyaniline.