Cusp of Non-Gaussian Density of Particles for a Diffusing Diffusivity Model.

We study a two state "jumping diffusivity" model for a Brownian process alternating between two different diffusion constants, D+>D-, with random waiting times in both states whose distribution is rather general. In the limit of long measurement times, Gaussian behavior with an effective diffusion coefficient is recovered. We show that, for equilibrium initial conditions and when the limit of the diffusion coefficient D-⟶0 is taken, the short time behavior leads to a cusp, namely a non-analytical behavior, in the distribution of the displacements P(x,t) for x⟶0. Visually this cusp, or tent-like shape, resembles similar behavior found in many experiments of diffusing particles in disordered environments, such as glassy systems and intracellular media. This general result depends only on the existence of finite mean values of the waiting times at the different states of the model. Gaussian statistics in the long time limit is achieved due to ergodicity and convergence of the distribution of the temporal occupation fraction in state D+ to a δ-function. The short time behavior of the same quantity converges to a uniform distribution, which leads to the non-analyticity in P(x,t). We demonstrate how super-statistical framework is a zeroth order short time expansion of P(x,t), in the number of transitions, that does not yield the cusp like shape. The latter, considered as the key feature of experiments in the field, is found with the first correction in perturbation theory.

Hitchhiker model for Laplace diffusion processes.

Brownian motion is a Gaussian process describing normal diffusion with a variance increasing linearly with time. Recently, intracellular single-molecule tracking experiments have recorded exponentially decaying propagators, a phenomenon called Laplace diffusion. Inspired by these developments we study a many-body approach, called the Hitchhiker model, providing a microscopic description of the widely observed behavior. Our model explains how Laplace diffusion is controlled by size fluctuations of single molecules, independently of the diffusion law which they follow. By means of numerical simulations Laplace diffusion is recovered and we show how single-molecule tracking and data analysis, in a many-body system, is highly nontrivial as tracking of a single particle or many in parallel yields vastly different estimates for the diffusivity. We quantify the differences between these two commonly used approaches, showing how the single-molecule estimate of diffusivity is larger if compared to the full tagging method.

Nonlinear irreversible thermodynamics of single-molecule experiments.

Irreversible thermodynamics of single-molecule experiments subject to external constraining forces of a mechanical nature is presented. Extending Onsager's formalism to the nonlinear case of systems under nonequilibrium external constraints, we are able to calculate the entropy production and the general nonlinear kinetic equations for the variables involved. In particular, we analyze the case of RNA stretching protocols obtaining critical oscillations between different configurational states when forced by external means to remain in the unstable region of its free-energy landscape, as observed in experiments. We also calculate the entropy produced during these hopping events and show how resonant phenomena in stretching experiments of single RNA macromolecules may arise. We also calculate the hopping rates using Kramer's approach obtaining a good comparison with experiments.

Effect of elastic colored noise in the hopping dynamics of single molecules in stretching experiments.

The influence of colored noise induced by elastic fluctuations in single-molecule stretching experiments is theoretically and numerically studied. Unlike in the thermal white noise case currently considered in the literature, elastically induced hopping dynamics between folded and unfolded states is manifested through critical oscillations showing smaller end-to-end distance fluctuations (δx∼1.25nm) within the free energy wells corresponding to both states. Our results are derived by analyzing the elastic coupling between the Handle-Molecule-Handle system and the laser optical tweezers (LOT) array. It is shown that an Ornstein-Uhlenbeck process related to this elastic coupling may trigger the hopping transitions via a colored noise with an intensity proportional to the elastic constant of the LOT array. Evolution equations of the variables of the system were derived by using the irreversible thermodynamics of small systems recently proposed. Theoretical expressions for the corresponding stationary probability densities are provided and the viability of inferring the shape of the free energy from direct measurements is discussed.