Force probe

Experimental techniques based on the application of mechanical forces to single molecules in small assemblies have been applied to study the binding properties of biomolecules and their response to external mechanical manipulations. Among such techniques are atomic force microscopy (AFM), optical tweezers, biomembrane force probe, and surface force apparatus experiments (Binning et al., 1986 Block and Svoboda, 1994 Evans et ah, 1995 Israelachvili, 1992). These techniques have inspired us and others (see also the chapters by Eichinger et al. and by Hermans et al. in this volume) to adopt a similar approach for the study of biomolecules by means of computer simulations. 

Although extraction of lipids from membranes can be induced in atomic force apparatus (Leckband et al., 1994) and biomembrane force probe (Evans et al., 1991) experiments, spontaneous dissociation of a lipid from a membrane occurs very rarely because it involves an energy barrier of about 20 kcal/mol (Cevc and Marsh, 1987). However, lipids are known to be extracted from membranes by various enzymes. One such enzyme is phospholipase A2 (PLA2), which complexes with membrane surfaces, destabilizes a phospholipid, extracts it from the membrane, and catalyzes the hydrolysis reaction of the srir2-acyl chain of the lipid, producing lysophospholipids and fatty acids (Slotboom et al., 1982 Dennis, 1983 Jain et al., 1995). SMD simulations were employed to investigate the extraction of a lipid molecule from a DLPE monolayer by human synovial PLA2 (see Eig. 6b), and to compare this process to the extraction of a lipid from a lipid monolayer into the aqueous phase (Stepaniants et al., 1997). 

GRIN/GRID nonbonded force probe of active sites Eran-cisco Molecular Discovery, Ltd. (Goodford)... 

Tamayo, J. and Garcia, R., Relationship between phase shift and energy dissipation in tapping-mode scanning force microscopy. Appl Phys. Lett., 73(20), 2926-2928 (1998). Gotsmann, B., Seidel, C., Anezykowski, B. and Fuchs, H., Conservative and dissipative tip-sample interaction forces probed with dynamic AFM. Phys. Rev. B Condens. Matter, 60, 11051-11061 (1999). 

The size, the velocity, and the solid volume fraction of the bubbles and the solids slugs are reflected in the shape and frequency of the force probe response as shown in Fig. 24. The amplitude of the oscillations is a measure of the solid slug velocity and solid volume fraction. Inside the bubbles, the probe response is nearly flat because of the negligible solids fraction inside the bubble. The spread of the peaks and the length of the flat portions of the probe responses are measures of the size and velocity of the solid slugs and gas bubbles respectively. 

Figure 24. Typical local bed density fluctuations as measured by the force probe.

Table 1. Average Bubble Rise Velocities (m/s) Calculated from the Force Probe Measurements and Comparison with Results from the Movies 40.6-cm Diameter Jet Assembly...

Solids Circulation Pattern. Yang et al. (1986) have shown that, based on the traversing force probe responses, three separate axial solids flow patterns can be identified. In the central core of the bed, the solid flow direction is all upward, induced primarily by the action of the jets and the rising bubbles. In the outer regions, close to the vessel walls, the solid flow is all downward. A transition zone, in which the solids move alternately upward and downward, depending on the approach and departure of the large bubbles, was detected in between these two regions. 

The solids circulation patterns were investigated with a force probe developed in-house. Typical force probe responses are presented in Figs. 43 and 44 for a probe located at 0.13 m from the jet nozzle and with different penetrations into the bed for an air tube velocity of 45.7 m/s. Sincetheforce probe is directional, the upward solids movement will produce a positive response from the probe and vice versa, the magnitude of the response being an indication of the magnitude of solids circulation rate. The number of major peaks per unit time is closely related to the actual bubble frequency in the bed. 

Figure 43. Force probe responses for probe penetration from 0.05 m to 0.30 m— 0.13 m from jet nozzle elevation, 46 m/s jet velocity, no solid feed.

Figure 45. Three major solids flow regions in 3-m model derived from force probe signal. 

Zapotoczny S, Auletta T, de Jong MR, Schonherr H, Huskens J, van Veggel FCJM, Reinhoudt DN, Vancso GJ. Chain length and concentration dependence of p-cyclodextrin-ferrocene host-guest complex rupture forces probed by dynamic force spectroscopy. Langmuir 2002 18 6988-6994. 

The diagrams in Fig. llc-f can be measured by the force probe method, when the amplitude and phase are measured as the tip approaches and retracts the surface vertically. In the non-contact range, both the amplitude and the phase retain their constant values (Fig. llc,e). When the tip enters the intermittent contact range (Zphase reduces almost linearly on approaching the surface. The deviation of the amplitude signal from a certain set-point value As is used by a feedback loop to maintain the separation Zc between the tip and sample constant, and hereby visualise the surface structure. When the surface composition is uniform, the amplitude variation is mainly caused by the surface topography. However, if the surface is heterogeneous, the variation in the amplitude can be affected by local differences in viscoelasticity [108-110 ] and adhesion [111] of the sample (Sect. 2.2.2). 

Quantitative evaluation of a force-distance curve in the non-contact range represents a serious experimental problem, since most of the SFM systems give deflection of the cantilever versus the displacement of the sample, while the experimentalists wants to obtain the surface stress (force per unit contact area) versus tip-sample separation. A few prerequisites have to be met in order to convert deflection into stress and displacement into tip-sample separation. First, the point of primary tip-sample contact has to be determined to derive the separation from the measured deflection of the cantilever tip and the displacement of the cantilever base [382]. Second, the deflection can be converted into the force under assumption that the cantilever is a harmonic oscillator with a certain spring constant. Several methods have been developed for calibration of the spring constant [383,384]. Third, the shape of the probe apex as well as its chemical structure has to be characterised. Spherical colloidal particles of known radius (ca. 10 pm) and composition can be used as force probes because they provide more reliable and reproducible data compared to poorly defined SFM tips [385]. 

Concerning properties, SFM has become a unique technique in probing local adhesion, friction and elastic response of various materials. This is based on the ability to measure forces as small as picoNewtons and probe areas well below 100 nm. The peculiar sensitivity of the force probe to different types of static and dynamic interactions provides a great number of contrast mechanisms which can map the surface structure regarding the chemical composition and physical properties. However, in most SFM measurements the interpretation of the surface maps remain to be very intricate, mostly because of the concurrent contribution of different forces into the net force. The progress in this field relies on new developments in technique which would allow to measure the properties like stiffness, adhesion, friction and viscosity, separately. 

Furthermore, a rigid glass bead can be glued to a tipless cantilever, and used as a force probe to compress single particles, such as Jurket T lymphomas cells (Lulevich et al., 2006) and polyelectrolyte microcapsules (Lulevich et al., 2003). 

In the present paper we extend our analysis of the experimental results obtained from this small deformation regime and we show that the result found by Reissner for the deformation of shallow spherical caps represents an excellent analytical approximation for the interpretation of the measurements. This result is varified by finite element modelling (FEM) and by experimental variation of the force probe geometry and radius as well as wall thickness of the studied capsules. This result is also applicable for other capsule deformation measurements, since it is independent of the specific Young s modulus. Furthermore, we report on speed dependent measurements that indicate the glassy nature of PAH/PSS multilayers. 

We begin with an abstract of the physics that underlies the kinetics of bond dissociation and structural transitions in a liquid environment. Developed from Einstein s theory of Brownian motion, these well-known concepts take advantage of the huge gap in time scale that separates rapid thermal impulses in liquids (< 10 s) from slow processes in laboratory measurements (e.g. from 10 s to min in the case of force probe tests). Three equivalent formulations describe molecular kinetics in an overdamped liquid environment. The first is a microscopic perspective where molecules behave as particles with instantaneous positions or states x(t) governed by an overdamped Langevin equation of motion,... 

B. A. Heymann and H. Grubmiiller (2001) Molecular dynamics force probe simulations of antibody/antigen unbinding Entropic control and nonadditivity of unbinding forces. Biophys. J. 81, pp. 1295-1313... 

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