Single molecule experiments in biophysics: exploring the thermal behavior of nonequilibrium small systems

Diverse physical systems are characterized by their response to small perturbations. Near thermodynamic equilibrium, the fluctuation-dissipation theorem provides a powerful theoretical and experimental tool to determine the nature of response by observing spontaneous equilibrium fluctuations. In this spirit, we derive here a collection of equalities and inequalities valid arbitrarily far from equilibrium that constrain the response of nonequilibrium steady states in terms of ...

A main goal of single-molecule experiments is to evaluate equilibrium free energy differences by applying fluctuation relations to repeated work measurements along irreversible processes. We quantify the error that is made in a free energy estimate by means of the Jarzynski equality when the accumulated work expended on the whole system (including the instrument) is erroneously replaced by the work transferred to the subsystem consisting of the sole molecular construct. We fi...

We present a method for determining the free energy of coexisting states from irreversible work measurements. Our approach is based on a fluctuation relation that is valid for dissipative transformations in partially equilibrated systems. To illustrate the validity and usefulness of the approach, we use optical tweezers to determine the free energy branches of the native and unfolded states of a two-state molecule as a function of the pulling control parameter. We determine, ...

This is an extended abstract of lectures delivered at the 4th Warsaw Summer School on Statistical Physics in Kazimierz Dolny, June 25-July 2, 2011.

There has been great interest in applying the results of statistical mechanics to single molecule experiements. Recent work has highlighted so-called non-equilibrium work-energy relations and Fluctuation Theorems which take on an equilibrium-like (time independent) form. Here I give a very simple heuristic example where an equilibrium result (the barometric law for colloidal particles) arises from theory describing the {\em thermodynamically} non-equilibrium phenomenon of a s...

The main physical features and operating principles of isothermal nanomachines in microworld are reviewed, which are common for both classical and quantum machines. Especial attention is paid to the dual and constructive role of dissipation and thermal fluctuations, fluctuation-dissipation theorem, heat losses and free energy transduction, thermodynamic efficiency, and thermodynamic efficiency at maximum power. Several basic models are considered and discussed to highlight ge...

Concepts of everyday use like energy, heat, and temperature have acquired a precise meaning after the development of thermodynamics. Thermodynamics provides the basis for understanding how heat and work are related and with the general rules that the macroscopic properties of systems at equilibrium follow. Outside equilibrium and away from macroscopic regimes most of those rules cannot be applied directly. Here we present recent developments that extend the applicability of t...

We introduce from an experimental point of view the main concepts of fluctuation theorems for work, heat and entropy production in out of equilibrium systems. We will discuss the important difference between the applications of these concepts to stochastic systems and to a second class of systems (chaotic systems) where the fluctuations are induced either by chaotic flows or by fluctuating driving forces. We will mainly analyze the stochastic systems using the measurements pe...

The Jarzynski equality and the fluctuation theorem relate equilibrium free energy differences to non-equilibrium measurements of the work. These relations extend to single-molecule experiments that have probed the finite-time thermodynamics of proteins and nucleic acids. The effects of experimental error and instrument noise have not previously been considered. Here, we present a Bayesian formalism for estimating free-energy changes from non-equilibrium work measurements that...

The laws of thermodynamics apply to biophysical systems on the nanoscale as described by the framework of stochastic thermodynamics. This theory provides universal, exact relations for quantities like work, which have been verified in experiments where a fully resolved description allows direct access to such quantities. Complementary studies consider partially hidden, coarse-grained descriptions, in which the mean entropy production typically is not directly accessible but c...