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Evaluation of commercially available blood pressure meters is performed. The effect of biophysical processes occurring in blood flow on indirect measurements of blood pressure is analysed. Some conclusions are given.
This work gives a thermodynamic analysis of outgrowth extraction from the cell body by a pulling force. The results are applied for a case when the pulling force is generated by an external high-frequency electric field. Two equilibrium conditions are analyzed: internal equilibrium of an outgrowth and equilibrium between the outgrowth and the cell body. In both cases the stability of feasible equilibrium states was studied. The work shows that the curvature of an outgrowth equilibrated with a pulling electric force depends on the squared amplitude of the electric field E0(2), on the outgrowth length l and on the transmembrane pressure differential delta P, and that at a sufficiently large transmembrane pressure differential the cylindrical form of the outgrowth loses its stability. Long outgrowths are more stable than short ones. The minimal value of critical pressure differential was estimated. The work also shows that outgrowth extraction from the cell body requires that the applied force exceeds a critical value below which no outgrowth is formed. The value of the electric field at which outgrowth formation is feasible was estimated.
Skiers, coaches, and sports scientists must work within mechanical constraints to improve performance. If Nordic skiing is to be improved by mechanical means, it will be achieved by affecting one or more of the major constraints: gravity, mass, friction, aerodynamic or hydrodynamic lift and drag, and centripetal force. For example, the skier who assumes a tucked position, drafts a competitor, and wears a drag-reducing hood and body suit is reducing aerodynamic constraints. Sliding friction may also be reduced by using specially prepared skis and by selecting skis appropriate for the snow characteristics of the race course. Skin friction hydrodynamic drag may also be affected by ski selection and by special base preparations. Gravity and mass constraints are diminished by using lightweight components, by carrying them in the least costly way, and by minimizing swing weight. The toppling effect of centripetal forces is addressed by leaning into turns. All of these examples address mechanical constraints in a way that reduces physical power requirements, and thus decrease the metabolic power required to ski at a given speed, as well as increasing the maximal speed attainable.
Standardized reproducible tests have been developed to determine the biomechanical performance of cardiovascular needles. The parameters used to assess performance were: 1) sharpness, 2) resistance to bending, and 3) ductility. Four comparable groups of tapercut and taper point cardiovascular needles were selected from different manufacturers for these biochemical studies. The results of this testing demonstrated that needle geometry, needle composition, and the manufacturer were important determinants of needle performance. When comparable needles were evaluated, the biochemical performance of cardiovascular needles manufactured by Ethicon, Inc. (Somerville, NJ) were superior to needles produced by other manufacturers. The superior performance characteristics of the cardiovascular needles produced by Ethicon, Inc. were related to their unique stainless steel alloy, American Society for Testing Materials 45500, which has greater yield and tensile strengths than the alloy used by the other manufacturers. This stainless steel alloy was ideal for the production of tapercut needles, which combined some of the features of a reverse cutting edge needle and taper point needle. Its very short cutting edges allowed it to penetrate the membrane at considerably lower penetration forces than were encountered with comparable taper point needles. In addition, the investigation indicated that the trocar point cardiovascular needles produced a large triangular defect whose diameter was much larger than that of the needle body. For this reason, the use of the trochar point needle is not recommended in cardiovascular surgery.
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Three penetration tests were obtained from corresponding locations at each condyle of 19 proximal tibiae. The patterns of condylar cancellous bone strength varied little between knees. The medial condyle was the strongest with an average medial to lateral strength ratio of 1.9, and in most knees the medial condyle was strongest centrally while the lateral condyle was strongest posteriorly. The penetration strength at 5 successive 2 mm levels beneath the resected subchondral surface also showed a constant pattern of variation. Bone strength decreased significantly at first except at the posterolateral site, then tended to level off. The reduction of strength was most pronounced in the centre of the condyles. The penetration tests were good predictors of the static compressive strength of the proximal tibia. Correlation coefficients of approximately 0.90 were obtained indicating statistically highly significant correlations (p less than or equal to 0.00001). The tests were carried out with equipment developed for in vivo measurements of cancellous bone strength during total knee replacement. The findings confirm the close relationship of these investigations to conventional compression tests.
Technical limitations of some isokinetic dynamometers have called into question the validity of some data on human muscle mechanics. The Biodex dynamometer has been shown to minimize the impact artefact while permitting automatic gravity correction. This dynamometer was used to study quadriceps muscle torque and power generation in elite power (n = 6) and elite endurance (n = 7) athletes over 12 randomly assigned isokinetic velocities from 30 degrees.s-1 to 300 degrees.s-1. The angle at peak torque varied as a negative, linear function of angular velocity, with the average angle across test velocities being 59.5 degrees (SD 10.2 degrees). Power athletes developed greater peak torque at each angular velocity (P less than 0.05) and experienced a 39.7% decrement in torque over the velocity range tested. Endurance athletes encountered a 38.8% decline in peak torque. Torques measured at 60 degrees of knee flexion followed a similar trend in both groups; however the greatest torques were recorded at 60 degrees.s-1 rather than at 30 degrees.s-1. Leg extensor muscle power increased monotonically with angular velocity in both power (r2 = 0.728) and endurance athletes (r2 = 0.839); however these curves diverged significantly so that the power athletes produced progressively more power with each velocity increment. These inter group differences probably reflected a combination of natural selection and training adaptation.
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The statistical mechanics of cross-bridge action is considered in order to develop constitutive equations that express fiber tension as a function of degree of activation and time history of speed of contraction. The kinetic equation of A.F. Huxley (1) is generalized to apply to the partially activated state. The rate parameters of attachment and detachment, and cross-bridge compliance are assumed to be step functions of extension, x, with a finite number of discontinuities. This assumption enables integration of the kinetic equation and its moments with respect to x resulting in analytic equations from which x has been eliminated. When the constants in the rate parameters and the force function are chosen so that Hill's force-velocity relation and features of the transient kinetic and tension data can be fitted, the resulting cross-bridge mechanism is quite similar to the one proposed by Podolsky et al. (2). Because the derived constitutive equations simplify mathematical analysis, the influence of various cross-bridge parameters on the mechanical behavior of muscle fibers may be evaluated. For example (a) instantaneous elastic response (T0-T1) and the magnitude of rapid recovery (T2-T1) after a step length change can be adequately explained when the rate of attachment is assumed high for positive x. In that case T2 corresponds to the force generated by cross-bridges in the region of negative x. (b) Kinetic transients occur as a result of the jumps that exist in the distribution of attached cross-bridges during the isometric state. Because of the hyperbolic nature of the kinetic equation, these jumps propagate in the--x direction causing rapid changes in the speed of contraction. (c) When the number of actin sites available for attachment is assumed to depend on the degree of activation, computational results indicate that the speed of shortening is insensitive to the degree of activation at each relative load. (d) It is shown that during sinusoidal oscillation, the mean and second-order harmonics of the experimental force-time curve are strongly dependent on cross-bridge parameters. Therefore, significant information may be lost when the data is expanded into Fourier series and only the first term is considered.
Various amphipathic compounds have been found to activate mechanosensitive (MS) ion channels in the bacterium Escherichia coli. These results were interpreted qualitatively in terms of the bilayer couple hypothesis. Here we present a mathematical model that describes the results quantitatively. According to the model, the uneven partitioning of amphipaths between the monolayers of the cell membrane causes one monolayer to be compressed and the other expanded. Because the open probability (Po) of the E. coli channels increased independently of which monolayer the amphipaths partitioned into, the model suggests that Po of the MS channels is determined by the monolayer having higher tension. We derived a relation between Po and amphipath concentration. The kinetics of Po variation after exposure of the cell membrane to the amphipaths was calculated based on this relation. The results fit satisfactorily the experimental data obtained with the cationic amphipath chlorpromazine and with the anionic amphipath trinitrophenol. Experiments which should further test the predictions following from the model are discussed.
We have investigated the ability of the photoaffinity, nonnucleotide ATP analogues, 2-[(4-azido-2-nitrophenyl) amino] ethyl triphosphate (NANTP) and 2-[(4-azido-2-nitrophenyl) amino] propyl triphosphate (PrNANTP), to support active contraction in glycerinated rabbit psoas fibers. At millimolar concentrations, in the absence of calcium, both analogues relaxed fibers. In the presence of calcium, MgNANTP produced isometric tension and stiffness that were one-half to two-thirds the values obtained in MgATP. Maximum shortening velocity and the calcium-activated, myofibrillar catalyzed rate of hydrolysis were approximately the same for MgNANTP as for MgATP. With MgNANTP as the substrate, increasing concentrations of the diphosphate analogue, MgNANDP, inhibited shortening velocity but did not change isometric tension. The addition of increased concentrations of orthophosphate (P) decreased tension while shortening velocity increased. Thus, the effects of the hydrolysis products of NANTP were quite similar to those observed previously for ADP and P in the presence of MgATP. Taken together, these observations show that MgNANTP binds to, and functions in the active site of myosin in a manner quite analogous to MgATP. Thus, the aryl azido group should serve as a valid photoaffinity label for the purine portion of the active site. In contrast, MgPrNANTP, which differs from MgNANTP only in an extra CH2 spacer between the nitrophenyl ring and the triphosphate moiety did not support isometric tension or active shortening in the presence of calcium. Fiber stiffness increased in the presence of calcium and MgPrNANTP, with a calcium-activated, myofibrillar MgPrNANTPase which was about half that obtained with MgATP. Thus, in the presence of MgPrNANTP, cross-bridges appeared to be cycling through states that were attached to actin, but not producing force.
We report the first time-resolved x-ray diffraction studies on tetanized intact single muscle fibers of the frog. The 10, 11, 20, 21, 30, and Z equatorial reflections were clearly resolved in the relaxed fiber. The preparation readily withstood 100 1-s duration (0.4-s beam exposure) tetani at 4 degrees C (less than 4% decline of force and no deterioration in the 10, 11 equatorial intensity ratio at rest or during activation). Equatorial intensity changes (10 and 11) and fiber stiffness led tension (t1/2 lead 20 ms at 4 degrees C) during the tetanus rise and lagged during the isometric phase of relaxation. These findings support the existence of a low force cross-bridge state during the rise of tetanic tension and isometric relaxation that is not evident at the tetanus plateau. In "fixed end" tetani lattice expansion occurred with a time course similar to stiffness during the tetanus rise. During relaxation, lattice spacing increased slightly, while the sarcomere length remained isometric, but underwent large changes after the "shoulder" of tension. Under length clamp control, lattice expansion during the tetanus rise was reduced or abolished, and compression (2%) of the lattice was observed. A lattice compression is predicted by certain cross-bridge models of force generation (Schoenberg, M. 1980. Biophys. J. 30:51-68; Schoenberg, M. 1980. Biophys. J. 30:69-78).
To explain the ability of some mechanosensitive cells to reverse the process of mechanotransduction and to generate mechanical oscillations and emit sound, a piezo-conformational coupling model (PCC model) is proposed. The model includes a transport protein which changes either its volume (PV-coupling) or its area in the membrane (gamma A-coupling) when undergoing conformational transitions. Such a protein can interact with an oscillating pressure to pump ions and create a transmembrane gradient if the affinities of the protein for ions are different at the two sides of membrane. The frequency and concentration windows for mechanical energy transduction were determined. Under optimal conditions, the efficiency of energy transduction can approach the theoretical maximum of 100%. If the concentration gradient exceeds the static head value (quasi-equilibrium which can be built up and maintained by this transport system), the energy transduction reverses and the transporter becomes a generator of mechanical oscillations at the expense of a concentration gradient. Estimation of thermodynamic parameters of the pump shows that the PV-coupling model would require large pressure oscillations to work while the gamma A-coupling model could work in physiological conditions. The gamma A-coupling mechanism may be used by cells for two purposes. In the reverse mode, it can be a force generator for various applications. In the direct mode, it may serve bioenergetic purposes by harvesting the energy of mechanical oscillations and storing it in the form of a concentration gradient. This pump has an unusual thermodynamic feature: it can distinguish the two components of the electrochemical potential gradient,i.e., the concentration gradient and the electrical potential, the latter serving as a permissive switch to open, or close, the pump when the potential reaches the threshold value.Predictions of the PCC model and its probable involvement in biological mechanotransduction are dicussed.
The receptor-mediated adhesion of cells to ligand-coated surfaces in viscous shear flow is an important step in many physiological processes, such as the neutrophil-mediated inflammatory response, lymphocyte homing, and tumor cell metastasis. This paper describes a calculational method which simulates the interaction of a single cell with a ligand-coated surface under flow. The cell is idealized as a microvilli-coated hard sphere covered with adhesive springs. The distribution of microvilli on the cell surface, the distribution of receptors on microvilli tips, and the forward and reverse reaction between receptor and ligand are all simulated using random number sampling of appropriate probability functions. The velocity of the cell at each time step in the simulation results from a balance of hydrodynamic, colloidal and bonding forces; the bonding force is derived by summing the individual contributions of each receptor-ligand tether. The model can simulate the effect of many parameters on adhesion, such as the number of receptors on microvilli tips, the density of ligand, the rates of reaction between receptor and ligand, the stiffness of the resulting receptor-ligand springs, the response of springs to strain, and the magnitude of the bulk hydrodynamic stresses. The model can successfully recreate the entire range of expected and observed adhesive phenomena, from completely unencumbered motion, to rolling, to transient attachment, to firm adhesion. Also, the method can generate meaningful statistical measures of adhesion, including the mean and variance in velocity, rate constants for cell attachment and detachment, and the frequency of adhesion. We find a critical modulating parameter of adhesion is the fractional spring slippage, which relates the strain of a bond to its rate of breakage; the higher the slippage, the faster the breakage for the same strain. Our analysis of neutrophil adhesive behavior on selectin-coated (CD62-coated) surfaces in viscous shear flow reported by Lawrence and Springer (Lawrence, M.B., and T.A. Springer 1991. Cell. 65:859-874) shows the fractional spring slippage of the CD62-LECAM-1 bond is likely below 0.01. We conclude the unique ability of this selectin bond to cause neutrophil rolling under flow is a result of its unique response to strain. Furthermore, our model can successfully recreate data on neutrophil rolling as function of CD62 surface density.
To describe the resistance of a bilayer to changes in curvature two mechanisms are distinguished which are termed bilayer couple bending and single-layer bending. In bilayer couple bending, the resistance arises from the 2-D isotropic elasticity of the two layers and their fixed distance. Single-layer bending covers the intrinsic bending stiffness of each monolayer. The two mechanisms are not independent. Even so, the distinction is useful since bilayer couple bending can relax by a slip between the layers from the local to the global fashion. Therefore, the bending stiffness of a bilayer depends on the time scale and on the extent of the deformation imposed on the membrane. Based on experimental data, it is shown by order of magnitude estimates that (a) the bending stiffness determined from thermally induced shape fluctuations of almost spherical vesicles is dominated by single-layer bending; (b) in the tether experiment on lipid vesicles and on red cells, a contribution of local bilayer couple bending can not be excluded; and (c) at the sharp corners at the leading and the trailing edge of tanktreading red cells, local bilayer couple bending appears to be important.
There have been very few studies which have measured the physical forces generated by cells during active movements. A special micropipette system has been designed to make it possible to observe cell motion within the pipette and to apply a pressure to counter the chemotactic migration of the cell. This provides a direct measure of the locomotion force generated by the cell. The average velocity of forward motion is 0.33 microns/s in the absence of counter-pressure. The application of a positive counter-pressure (C-P) causes a decrease in the velocity of the forward motion of the cell. At 17 cm H2O of C-P, the cell velocity drops to zero and even moves backward with a higher C-P. The results show that the decrement of velocity is linearly related to the magnitude of the C-P with a complete stoppage at a pressure of 17 cm H2O which corresponds to a force of 0.003 dyn. The maximum work rate of the cell is approximately 2.5 x 10(-8) erg/s.
The incompressibility of the lipid bilayer keeps the total surface area of the red cell membrane constant. Local conservation of membrane surface area requires that each surface element of the membrane skeleton keeps its area when its aspect ratio is changed. A change in area would require a flow of lipids past the intrinsic proteins to which the skeleton is anchored. in fast red cell deformations, there is no time for such a flow. Consequently, the bilayer provides for local area conservation. In quasistatic deformations, the extent of local change in surface area is the smaller the larger the isotropic modulus of the skeleton in relation to the shear modulus. Estimates indicate: (a) the velocity of relative flow between lipid and intrinsic proteins is proportional to the gradient in normal tension within the skeleton and inversely proportional to the viscosity of the bilayer; (b) lateral diffusion of lipids is much slower than this flow; (c) membrane tanktreading at frequencies prevailing in vivo as well as the release of a membrane tongue from a micropipette are fast deformations; and (d) the slow phase in micropipette aspiration may be dominated by a local change in skeleton surface.