The biochemical cycle of a molecular motor provides the essential link between its thermodynamics and kinetics. The thermodynamics of the cycle determine the motor's ability to perform mechanical work, whilst the kinetics of the cycle govern its stochastic behaviour. We concentrate here on tightly coupled, processive molecular motors, such as kinesin and myosin V, which hydrolyse one molecule of ATP per forward step. Thermodynamics require that, when such a motor pulls against a constant load f, the ratio of the forward and backward products of the rate constants for its cycle is exp [-(DeltaG + u(0)f)/kT], where -DeltaG is the free energy available from ATP hydrolysis and u(0) is the motor's step size. A hypothetical one-state motor can therefore act as a chemically driven ratchet executing a biased random walk. Treating this random walk as a diffusion problem, we calculate the forward velocity v and the diffusion coefficient D and we find that its randomness parameter r is determined solely by thermodynamics. However, real molecular motors pass through several states at each attachment site. They satisfy a modified diffusion equation that follows directly from the rate equations for the biochemical cycle and their effective diffusion coefficient is reduced to D-v(2)tau, where tau is the time-constant for the motor to reach the steady state. Hence, the randomness of multistate motors is reduced compared with the one-state case and can be used for determining tau. Our analysis therefore demonstrates the intimate relationship between the biochemical cycle, the force-velocity relation and the random motion of molecular motors.
Molecular motors are the fundamental agents of movement in living organisms. A prime example is the actomyosin motor that powers muscle contraction. We illustrate the remarkable physics of this motor using a simplified three-state model, in which a myosin cross-bridge attaches to an actin filament, tilts over and then detaches. This `cross-bridge cycle', driven by ATP hydrolysis, is similar to a thermodynamic cycle, except that the molecular system is stochastic. Random transitions in the cycle therefore produce tension fluctuations, which have recently been observed in single-molecule experiments. Furthermore, since the rate constants for attachment and tilting depend on the elastic energy in the cross-bridge spring, the molecular motor is a highly nonlinear mechanical system. A bias tension `stretch activates' the motor, and it then develops the remarkable property of `negative viscosity', which allows it to perform as a self-sustained mechanical oscillator. However, when a series of attachment sites is available, the motor operates instead as a ratchet, pulling the actin filament rapidly forwards against a light load, whilst a heavy load pulls the filament only very slowly in the opposite direction. Similar ideas may apply to the dynein-tubulin motor that powers cilia and flagella and the kinesin-tubulin motor used in intracellular transport.
A survey was undertaken to determine the importance of confidentiality of sexual health clinics to young people, and their preferences for service provision. A questionnaire was given to school attenders in year 9 (age 13-14 years) at four comprehensive schools. Class leaders assisted students with literacy or language difficulties. Two hundred and ninety five questionnaires were distributed and all were returned (male 143 (48.5%), female 152 (51.5%). In all 199 (67.5%) had never used sexual health services. The importance of confidentiality (asked in two differently worded questions) was rated as 8.84 and 8.59 (mean) on a scale of 1 (not important) to 10 (very important), 166 (56.3%) rated confidentiality as most important feature of service and 254 (86.1%) were more likely to use a service if it was confidential; 161 (54.6%) would not use service if it were not confidential. Two hundred and sixty-six (90.2%) would give honest answers in a confidential service; 186 (63.1%) would not attend if they thought that child protection services would be informed; 136 (46.1%) would not want general practitioner informed of attendance; 209 (70.8%) would like regular sexual health check ups; 150 (50.8%) would prefer a young people clinic, but only 105 (35.6%) prefer a 'one-stop shop'. This study shows that confidentiality is extremely important to young people considering using a sexual health service. It is the first UK study to show that if confidentiality is lost, young people may not attend, or may not be honest when they utilize a sexual health service. This is particularly relevant at the moment in light of the threat to confidentiality for young people attending sexual health services.
We have studied the diffraction of a focussed laser beam by single fibres of glycerinated rabbit psoas muscle as a function of the angle of incidence. Diffraction efficiencies as high as 34% were observed at the first-order Bragg angle, indicative of well-ordered striated fibres with a strong periodic modulation of the refractive index. A theory is presented to account for our observations based upon the coupled-wave model developed by Kogelnik (1967) and Magnusson and Gaylord (1977) for the description of thick phase gratings in holography. We have solved the coupled-wave equations on a computer using a realistic index modulation taken from the measurements of Huxley and Hanson (1957). Comparison of theory with experiment shows that coupled-wave effects are indeed present in well-ordered muscle fibres, and the observed diffraction efficiency is in quite good agreement with what would be expected theoretically. Most importantly, the computer model allows us to calculate the diffraction efficiency for curved striations, which are observed for real muscle fibres under a microscope. The sensitivity of the diffraction efficiency to curvature of the striations may have implications for the interpretation of other optical experiments on muscle. We also consider the effects on our measurements of the focussing lens and refraction by the cylindrical fibre.
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