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.

Experimental Investigation of the Velocity Effect on Adhesion Forces with an Atomic Force Microscope Atomic Force Microscope

Capillary forces are significantly dominant in adhesive forces measured with an atomic force microscope (AFM) in ambient air, which are always thought to be dependent on water film thickness, relative humidity, and the free energy of water film. We study the nature of the pull-off force on a variety of surfaces as a function of tip velocity. It is found that the capillary forces are of relatively strong dependence on tip velocity. The present experiment is expected to provide a better understanding of the work mechanism of AFM in ambient air.

A comparison of winter pre-heating requirements for natural displacement and natural mixing ventilation

In winter, natural ventilation can be achieved either through mixing ventilation or upward displacement ventilation (P.F. Linden, The fluid mechanics of natural ventilation, Annual Review of Fluid Mechanics 31 (1999) pp. 201-238). We show there is a significant energy saving possible by using mixing ventilation, in the case that the internal heat gains are significant, and illustrate these savings using an idealized model, which predicts that with internal heat gains of order 0.1 kW per person, mixing ventilation uses of a fraction of order 0.2-0.4 of the heat load of displacement ventilation assuming a well-insulated building. We then describe a strategy for such mixing natural ventilation in an atrium style building in which the rooms surrounding the atrium are able to vent directly to the exterior and also through the atrium to the exterior. The results are motivated by the desire to reduce the energy burden in large public buildings such as hospitals, schools or office buildings centred on atria. We illustrate a strategy for the natural mixing ventilation in order that the rooms surrounding the atrium receive both pre-heated but also sufficiently fresh air, while the central atrium zone remains warm. We test the principles with some laboratory experiments in which a model air chamber is ventilated using both mixing and displacement ventilation, and compare the energy loads in each case. We conclude with a discussion of the potential applications of the approach within the context of open plan atria type office buildings.

On the transition from displacement to mixing ventilation with a localized heat source

We investigate the steady state natural ventilation of a room heated at the base and consisting of two vents at different levels. We explore how the air flow rate and internal temperature relative to the exterior vary as a function of the vent areas, position of the vents and heat load in order to establish appropriate ventilation strategies for a room. When the room is heated by a distributed source, the room becomes well mixed and the steady state ventilation rate depends on the heating rate, the area of the vents and the distance between the lower and upper level vents. However, when the room is heated by a localised source the room becomes stratified. If the effective ventilation area is sufficiently large, then the interface separating the two layers lies above the inlet vent and the lower layer is comprised of ambient fluid. In this case the upper layer is warmer than in the well mixed case and the ventilation rate is smaller. However, if the effective area for ventilation is sufficiently small, then the interface separating the two layers lies below the inlet vent and the lower layer is comprised of warm fluid which originates as the cold incoming fluid mixes during descent from the vent through the upper layer. In this case both the ventilation rate and the upper layer temperature are the same as in the case of a distributed heat load. As the vertical separation between lower and upper level vents decreases, then the temperature difference between the layers falls to zero and the room becomes approximately well mixed. These findings suggest how the appropriate ventilation strategy for a room can be varied depending on the exterior temperature, with mixing ventilation more suitable for winter conditions and displacement ventilation for warmer external temperatures.

Competitive protein adsorption studied with atomic force microscopy and imaging ellipsometry

The adsorption and competitive adsorption of collagen and bovine serum albumin (BSA) were directly visualized and quantified using atomic force microscopy (AFM) and imaging ellipsometry. Chemically modified silicon surfaces were used as hydrophilic and hydrophobic substrates. The results showed that collagen and BSA in single component solution adsorbed onto a hydrophobic surface two times more than that onto a hydrophilic surface. The competitive adsorption between collagen and BSA showed that serum albumin preferentially adsorbed onto a hydrophobic surface, while collagen on a hydrophilic surface. In the binary solution of BSA (1 mg/ml BSA) and collagen (0.1 mg/ml), nearly 100% of the protein adsorbed onto the hydrophobic surface was BSA, but on the hydrophilic surface only about 6% was BSA. Surface affinity was the main factor controlling the competitive adsorption.

ZnO film based surface acoustic wave micro-pump

In this study, a micro-pump unit based on surface acoustic wave (SAW) on piezoelectric ZnO film is designed and fabricated as a micro-fluidic device. It employs a mechanical wave, which is generated electrically using an aluminum interdigital transducer (IDT), and propagates on the surface of the ZnO film. The ZnO film was used in this study because it has a high electromechanical coefficient and an excellent bonding with various substrate materials, in particular silicon. The sputtering parameters for ZnO film deposition have been optimized, and the ZnO films with different thickness from 1 micron to 5.5 microns were prepared. The film properties have been characterized using different methods, such as scanning electron microscopy, X-ray diffraction and atomic force microscopy. Aluminum IDT with a finger width and spacing of 8 microns was patterned on the ZnO film using a lift-off process. The frequency generated was measured using a network analyzer, and it varies from 130 MHz to 180 MHz as a function of film thickness. A signal generator was used to generate the frequency with a power amplifier to amplify the signal, which was then applied to aluminum IDT to generate the surface acoustic wave. If a liquid droplet exists on the surface carrying the acoustic wave, the energy and the momentum of the SAW will be coupled into the fluid, causing the liquid to vibrate and move on film surface. The strength of this movement is determined by the applied voltage and frequency. The volume of the liquid drop loaded on the SAW device in this study is of several hundreds of nanoliters. The movement of the liquid inside the droplet and also on the ZnO film surface can be demonstrated. The performance of ZnO SAW device was characterized as a function of film thickness. © 2007 IOP Publishing Ltd.

Studying Aggregate in Lysozyme Solution by Atomic Force Microscope

The aggregates in lysozyme solution with different NaCl concentration were investigated by Atomic Force Microscope (AFM). The AFM images show that there exist lysozyme monomers, n-mers and clusters in lysozyme solution when the conditions are not suitable for crystal growth. In favorable conditions for crystal growth, the lysozyme clusters disappear and almost only monomers exist in solution.

Equivalency and Locality in Nano-Scale Measurement

Two principal problems of equivalency and locality in nano-scale measurement are considered in this paper. The conventional measurements of force and displacement are always closely related to the equivalency problem between the measuremental results by experimental system and the real physical status of the sample, and the locality of the mechanical quantities to be measured. There are some noticeable contradictions in nano-scale measurements induced by the two problems. In this paper, by utilizing a coupled molecular-continuum method, we illustrate the important effects of the two principal problems in atomic force microscopy (AFM) measurements on nano-scale. Our calculations and analysis of these typical mechanical measurement problems suggest that in nano-meter scale measurements, the two principal problems must be carefully dealt with. The coupled molecular-continuum method used in this paper is very effective in solving these problems on nano-scale.

Mesofracture mechanics: a necessary link

Classical fracture mechanics is based on the premise that small scale features could be averaged to give a larger scale property such that the assumption of material homogeneity would hold. Involvement of the material microstructure, however, necessitates different characteristic lengths for describing different geometric features. Macroscopic parameters could not be freely exchanged with those at the microscopic scale level. Such a practice could cause misinterpretation of test data. Ambiguities arising from the lack of a more precise range of limitations for the definitions of physical parameters are discussed in connection with material length scales. Physical events overlooked between the macroscopic and microscopic scale could be the link that is needed to bridge the gap. The classical models for the creation of free surface for a liquid and solid are oversimplified. They consider only the translational motion of individual atoms. Movements of groups or clusters of molecules deserve attention. Multiscale cracking behavior also requires the distinction of material damage involving at least two different scales in a single simulation. In this connection, special attention should be given to the use of asymptotic solution in contrast to the full field solution when applying fracture criteria. The former may leave out detail features that would have otherwise been included by the latter. Illustrations are provided for predicting the crack initiation sites of piezoceramics. No definite conclusions can be drawn from the atomistic simulation models such as those used in molecular dynamics until the non-equilibrium boundary conditions can be better understood. The specification of strain rates and temperatures should be synchronized as the specimen size is reduced to microns. Many of the results obtained at the atomic scale should be first identified with those at the mesoscale before they are assumed to be connected with macroscopic observations. Hopefully, "mesofracture mechanics" could serve as the link to bring macrofracture mechanics closer to microfracture mechanics.

Casimir Effect on the Pull-in Parameters of Nanometer Switches

Casimir effect on the critical pull-in gap and pull-in voltage of nanoelectromechanical switches is studied. An approximate analytical expression of the critical pull-in gap with Casimir force is presented by the perturbation theory. The corresponding pull-in parameters are computed numerically, from which one can notice the nonlinear effect of Casimir force on the pull-in parameters. The detachment length has been presented, which increases with increasing thickness of the beam.

Methods of Obtaining Instantaneous Modulus of Viscoelastic Solids Using Displacement-Controlled Instrumented Indentation with Axisymmetric Indenters of Arbitrary Smooth Profiles

We derive a relationship between the initial unloading slope, contact depth, and the instantaneous relaxation modulus for displacement-controlled indentation in linear viscoelastic solids by a rigid indenter with an arbitrary axisymmetric smooth profile. While the same expression is well known for indentation in elastic and in elastic–plastic solids, we show that it is also true for indentation in linear viscoelastic solids, provided that the unloading rate is sufficiently fast. When the unloading rate is slow, a “hold” period between loading and unloading can be used to provide a correction term for the initial unloading slope equation. Finite element calculations are used to illustrate the methods of fast unloading and “hold-at-the-maximum-indenter-displacement” for determining the instantaneous modulus using spherical indenters.