Condensed Matter Theory

Abstract:

<jats:p>DNA–RNA hybrid strand displacement underpins the function of many natural and engineered systems. Understanding and controlling factors affecting DNA–RNA strand displacement reactions is necessary to enable control of processes such as CRISPR-Cas9 gene editing. By combining multiscale modeling with strand displacement experiments, we show that the distribution of bases within the displacement domain has a very strong effect on reaction kinetics, a feature unique to DNA–RNA hybrid strand displacement. Merely by redistributing bases within a displacement domain of fixed base composition, we are able to design sequences whose reaction rates span more than four orders of magnitude. We extensively characterize this effect in reactions involving the invasion of dsDNA by an RNA strand, as well as the invasion of a hybrid duplex by a DNA strand. In all-DNA strand displacement reactions, we find a predictable but relatively weak sequence dependence, confirming that DNA–RNA strand displacement permits far more thermodynamic and kinetic control than its all-DNA counterpart. We show that oxNA, a recently introduced coarse-grained model of DNA–RNA hybrids, can reproduce trends in experimentally observed reaction rates. We also develop a simple kinetic model for predicting strand displacement rates. On the basis of these results, we argue that base distribution effects may play an important role in natural R-loop formation and in the function of the guide RNAs that direct CRISPR-Cas systems.</jats:p>

Abstract:

The dynamics of many nanoscale biological and synthetic systems such as enzymes and molecular motors are activated by thermal noise, and driven out-of-equilibrium by local energy dissipation. Because the energies dissipated in these systems are comparable to the thermal energy, one would generally expect their dynamics to be highly stochastic. Here, by studying a thermodynamically-consistent model of two coupled noise-activated oscillators, we show that this is not always the case. Thanks to a novel phenomenon that we term topological phase locking (TPL), the coupled dynamics become quasi-deterministic, resulting in a greatly enhanced average speed of the oscillators. TPL is characterized by the emergence of a band of periodic orbits that form a torus knot in phase space, along which the two oscillators advance in rational multiples of each other. The effectively conservative dynamics along this band coexists with the basin of attraction of the dissipative fixed point. We further show that TPL arises as a result of a complex, infinite hierarchy of global bifurcations. Our results have implications for understanding the dynamics of a wide range of systems, from biological enzymes and molecular motors to engineered nanoscale electronic, optical, or mechanical oscillators.

Abstract:

The effect of hydrodynamic interactions on the nonequilibrium stochastic dynamics of particles - arising from the conservation of momentum in the fluid medium - is examined in the context of the relationship between fluctuations, response functions, and the entropy production rate. The multiplicative nature of the hydrodynamic interactions is shown to introduce subtleties that preclude a straightforward extension of the Harada-Sasa relation. A generalization of the definitions involved in the framework is used to propose a new form of the relation applicable to systems with hydrodynamic interactions. The resulting framework will enable characterization of the nonequilibrium properties of living and active matter systems, which are predominantly in suspensions.

Abstract: