Helicase processivity and not the unwinding velocity exhibits universal increase with force

Helicases, involved in a number of cellular functions, are motors that translocate along singlestranded nucleic acid and couple the motion to unwinding double-strands of a duplex nucleic acid. The junction between double and single strands creates a barrier to the movement of the helicase, which can be manipulated in vitro by applying mechanical forces directly on the nucleic acid strands. Single molecule experiments have demonstrated that the unwinding velocities of some helicases increase dramatically with increase in the external force, while others show little response. In contrast, the unwinding processivity always increases when the force increases. The differing responses of the unwinding velocity and processivity to force has lacked explanation. By generalizing a previous model of processive unwinding by helicases, we provide a unified framework for understanding the dependence of velocity and processivity on force and the nucleic acid sequence. We predict that the sensitivity of unwinding processivity to external force is a universal feature that should be observed in all helicases. Our prediction is illustrated using T7 and NS3 helicases as case studies. Interestingly, the increase in unwinding processivity with force depends on whether the helicase forces base pair opening by direct interaction or if such a disruption occurs spontaneously due to thermal uctuations. Based on the theoretical results, we propose that proteins like single-strand binding proteins associated with helicases in the replisome, may have co-evolved with helicases to increase the unwinding processivity even if the velocity remains unaffected

A lattice model of hydrophobic interactions

Hydrogen bonding is modeled in terms of virtual exchange of protons between water molecules. A simple lattice model is analyzed, using ideas and techniques from the theory of correlated electrons in metals. Reasonable parameters reproduce observed magnitudes and temperature dependence of the hydrophobic interaction between substitutional impurities and water within this lattice.Comment: 7 pages, 3 figures. To appear in Europhysics Letter

Refolding dynamics of stretched biopolymers upon force quench

Single molecule force spectroscopy methods can be used to generate folding trajectories of biopolymers from arbitrary regions of the folding landscape. We illustrate the complexity of the folding kinetics and generic aspects of the collapse of RNA and proteins upon force quench, using simulations of an RNA hairpin and theory based on the de Gennes model for homopolymer collapse. The folding time, $\tau_F$, depends asymmetrically on $\delta f_S = f_S - f_m$ and $\delta f_Q = f_m - f_Q$ where $f_S$ ($f_Q$) is the stretch (quench) force, and $f_m$ is the transition mid-force of the RNA hairpin. In accord with experiments, the relaxation kinetics of the molecular extension, $R(t)$, occurs in three stages: a rapid initial decrease in the extension is followed by a plateau, and finally an abrupt reduction in $R(t)$ that occurs as the native state is approached. The duration of the plateau increases as $\lambda =\tau_Q/\tau_F$ decreases (where $\tau_Q$ is the time in which the force is reduced from $f_S$ to $f_Q$). Variations in the mechanisms of force quench relaxation as $\lambda$ is altered are reflected in the experimentally measurable time-dependent entropy, which is computed directly from the folding trajectories. An analytical solution of the de Gennes model under tension reproduces the multistage stage kinetics in $R(t)$. The prediction that the initial stages of collapse should also be a generic feature of polymers is validated by simulation of the kinetics of toroid (globule) formation in semiflexible (flexible) homopolymers in poor solvents upon quenching the force from a fully stretched state. Our findings give a unified explanation for multiple disparate experimental observations of protein folding.Comment: 31 pages 11 figure

Effects of counterion fluctuations in a polyelectrolyte brush

We investigate the effect of counterion fluctuations in a single polyelectrolyte brush in the absence of added salt by systematically expanding the counterion free energy about Poisson-Boltzmann mean field theory. We find that for strongly charged brushes, there is a collapse regime in which the brush height decreases with increasing charge on the polyelectrolyte chains. The transition to this collapsed regime is similar to the liquid-gas transition, which has a first-order line terminating at a critical point. We find that for monovalent counterions the transition is discontinuous in theta solvent, while for multivalent counterions the transition is generally continuous. For collapsed brushes, the brush height is not independent of grafting density as it is for osmotic brushes, but scales linear with it.Comment: 9 pages, 9 figure

Analysis of electroencephalograms in Alzheimer's disease patients with multiscale entropy

The aim of this study was to analyse the electroencephalogram (EEG) background activity of Alzheimer’s disease (AD) patients using the Multiscale Entropy (MSE). The MSE is a recently developed method that quantifies the regularity of a signal on different time scales. These time scales are inspected by means of several coarse-grained sequences formed from the analysed signals. We recorded the EEGs from 19 scalp electrodes in 11 AD patients and 11 age-matched controls and estimated the MSE profile for each epoch of the EEG recordings. The shape of the MSE profiles reveals the EEG complexity, and it suggests that the EEG contains information in deeper scales than the smallest one. Moreover, the results showed that the EEG background activity is less complex in AD patients than control subjects. We found significant difference

Fluctuations of a driven membrane in an electrolyte

We develop a model for a driven cell- or artificial membrane in an electrolyte. The system is kept far from equilibrium by the application of a DC electric field or by concentration gradients, which causes ions to flow through specific ion-conducting units (representing pumps, channels or natural pores). We consider the case of planar geometry and Debye-H\"{u}ckel regime, and obtain the membrane equation of motion within Stokes hydrodynamics. At steady state, the applied field causes an accumulation of charges close to the membrane, which, similarly to the equilibrium case, can be described with renormalized membrane tension and bending modulus. However, as opposed to the equilibrium situation, we find new terms in the membrane equation of motion, which arise specifically in the out-of-equilibrium case. We show that these terms lead in certain conditions to instabilities.Comment: 7 pages, 2 figures. submitted to Europhys. Let