A lattice polymer study of DNA renaturation dynamics

DNA renaturation is the recombination of two complementary single strands to form a double helix. It is experimentally known that renaturation proceeds through the formation of a double stranded nucleus of several base pairs (the rate limiting step) followed by a much faster zippering. We consider a lattice polymer model undergoing Rouse dynamics and focus on the nucleation of two diffusing strands. We study numerically the dependence of various nucleation rates on the strand lengths and on an additional local nucleation barrier. When the local barrier is sufficiently high, all renaturation rates considered scale with the length as predicted by Kramers' rate theory and are also in agreement with experiments: their scaling behavior is governed by exponents describing equilibrium properties of polymers. When the local barrier is lowered renaturation occurs in a regime of genuine non-equilibrium behavior and the scaling deviates from the rate theory prediction.Comment: 13 pages, 6 figures. To appear in Journal of Statistical Mechanic

Breakdown of thermodynamic equilibrium for DNA hybridization in microarrays

Test experiments of hybridization in DNA microarrays show systematic deviations from the equilibrium isotherms. We argue that these deviations are due to the presence of a partially hybridized long-lived state, which we include in a kinetic model. Experiments confirm the model predictions for the intensity vs. free energy behavior. The existence of slow relaxation phenomena has important consequences for the specificity of microarrays as devices for the detection of a target sequence from a complex mixture of nucleic acids.Comment: 4 pages, 4 figure

The computational complexity of distance functions of two-dimensional domains

AbstractWe study the computational complexity of the distance function associated with a polynomial-time computable two-dimensional domains, in the context of the Turing machine-based complexity theory of real functions. It is proved that the distance function is not necessarily computable even if a two-dimensional domain is polynomial-time recognizable. On the other hand, if both the domain and its complement are strongly polynomial-time recognizable, then the distance function is polynomial-time computable if and only if P=NP

Anomalous zipping dynamics and forced polymer translocation

We investigate by Monte Carlo simulations the zipping and unzipping dynamics of two polymers connected by one end and subject to an attractive interaction between complementary monomers. In zipping, the polymers are quenched from a high temperature equilibrium configuration to a low temperature state, so that the two strands zip up by closing up a "Y"-fork. In unzipping, the polymers are brought from a low temperature double stranded configuration to high temperatures, so that the two strands separate. Simulations show that the unzipping time, $\tau_u$, scales as a function of the polymer length as $\tau_u \sim L$, while the zipping is characterized by anomalous dynamics $\tau_z \sim L^\alpha$ with $\alpha = 1.37(2)$. This exponent is in good agreement with simulation results and theoretical predictions for the scaling of the translocation time of a forced polymer passing through a narrow pore. We find that the exponent $\alpha$ is robust against variations of parameters and temperature, whereas the scaling of $\tau_z$ as a function of the driving force shows the existence of two different regimes: the weak forcing ($\tau_z \sim 1/F$) and strong forcing ($\tau_z$ independent of $F$) regimes. The crossover region is possibly characterized by a non-trivial scaling in $F$, matching the prediction of recent theories of polymer translocation. Although the geometrical setup is different, zipping and translocation share thus the same type of anomalous dynamics. Systems where this dynamics could be experimentally investigated are DNA (or RNA) hairpins: our results imply an anomalous dynamics for the hairpins closing times, but not for the opening times.Comment: 15 pages, 9 figure

Real-time optical manipulation of cardiac conduction in intact hearts

Optogenetics has provided new insights in cardiovascular research, leading to new methods for cardiac pacing, resynchronization therapy and cardioversion. Although these interventions have clearly demonstrated the feasibility of cardiac manipulation, current optical stimulation strategies do not take into account cardiac wave dynamics in real time. Here, we developed an all‐optical platform complemented by integrated, newly developed software to monitor and control electrical activity in intact mouse hearts. The system combined a wide‐field mesoscope with a digital projector for optogenetic activation. Cardiac functionality could be manipulated either in free‐run mode with submillisecond temporal resolution or in a closed‐loop fashion: a tailored hardware and software platform allowed real‐time intervention capable of reacting within 2 ms. The methodology was applied to restore normal electrical activity after atrioventricular block, by triggering the ventricle in response to optically mapped atrial activity with appropriate timing. Real‐time intraventricular manipulation of the propagating electrical wavefront was also demonstrated, opening the prospect for real‐time resynchronization therapy and cardiac defibrillation. Furthermore, the closed‐loop approach was applied to simulate a re‐entrant circuit across the ventricle demonstrating the capability of our system to manipulate heart conduction with high versatility even in arrhythmogenic conditions. The development of this innovative optical methodology provides the first proof‐of‐concept that a real‐time optically based stimulation can control cardiac rhythm in normal and abnormal conditions, promising a new approach for the investigation of the (patho)physiology of the heart

Optogenetics design of mechanistically-based stimulation patterns for cardiac defibrillation

Current rescue therapies for life-threatening arrhythmias ignore the pathological electro-anatomical substrate and base their efficacy on a generalized electrical discharge. Here, we developed an all-optical platform to examine less invasive defibrillation strategies. An ultrafast wide-field macroscope was developed to optically map action potential propagation with a red-shifted voltage sensitive dye in whole mouse hearts. The macroscope was implemented with a random-access scanning head capable of drawing arbitrarily-chosen stimulation patterns with sub-millisecond temporal resolution allowing precise epicardial activation of Channelrhodopsin2 (ChR2). We employed this optical system in the setting of ventricular tachycardia to optimize mechanistic, multi-barrier cardioversion/defibrillation patterns. Multiple regions of conduction block were created with a very high cardioversion efficiency but with lower energy requirements as compared to whole ventricle interventions to interrupt arrhythmias. This work demonstrates that defibrillation energies can be substantially reduced by applying discrete stimulation patterns and promotes the progress of current anti-arrhythmic strategies