The thermodynamic uncertainty relation provides an inequality relating any mean current, the associated dispersion and the entropy production rate for arbitrary non-equilibrium steady states. Applying it here to a general model of a molecular motor running against an external force or torque, we show that the thermodynamic efficiency of such motors is universally bounded by an expression involving only experimentally accessible quantities. For motors pulling cargo through a viscous fluid, a universal bound for the corresponding Stokes efficiency follows as a variant. A similar result holds if mechanical force is used to synthesize molecules of high chemical potential. Crucially, no knowledge of the detailed underlying mechano-chemical mechanism is required for applying these bounds.
Molecular motors power directed transport of cargoes within cells. Even if a single motor is sufficient to transport a cargo, motors often cooperate in small teams. We discuss the cooperative cargo transport by several motors theoretically and explore some of its properties. In particular we emphasize how motor teams can drag cargoes through a viscous environment.
The dynamics of molecular motors which occasionally detach from a heterogeneous track like DNA or RNA is considered. Motivated by recent single molecule experiments, we study a simple model for a motor moving along a disordered track using chemical energy while an external force opposes its motion. The motors also have finite processivity, i.e., they can leave the track with a position dependent rate. We show that the response of the system to disorder in the hopping off rate depends on the value of the external force. For most values of the external force, strong disorder causes the motors wh…
The effect of sequence heterogeneity on polynucleotide translocation across a pore and on simple models of molecular motors such as helicases, DNA polymerase/exonuclease and RNA polymerase is studied in detail. Pore translocation of RNA or DNA is biased due to the different chemical environments on the two sides of the membrane, while the molecular motor motion is biased through a coupling to chemical energy. An externally applied force can oppose these biases. For both systems we solve lattice models exactly both with and without disorder. The models incorporate explicitly the coupling to the…
Biological transport is supported by collective dynamics of enzymatic molecules that are called motor proteins or molecular motors. Experiments suggest that motor proteins interact locally via short-range potentials. We investigate the fundamental role of these interactions by analyzing a new class of totally asymmetric exclusion processes where interactions are accounted for in a thermodynamically consistent fashion. Theoretical analysis that combines various mean-field cal- culations and computer simulations suggests that dynamic properties of molecular motors strongly depend on interactions…
Understanding the operation of biological molecular motors, nanoscale machines that transduce electrochemical energy into mechanical work, is enhanced by bottom-up strategies to synthesize novel motors.
The effect of sequence heterogeneity on the dynamics of molecular motors is reviewed and analyzed using a set of recently introduced lattice models. First, we review results for the influence of heterogenous tracks such as a single-strand of DNA or RNA on the dynamics of the motors. We stress how the predicted behavior might be observed experimentally in anomalous drift and diffusion of motors over a wide range of parameters near the stall force and discuss the extreme limit of strongly biased motors with one-way hopping. We then consider the dynamics in an environment containing a variety of …
By considering subexponential contributions in large deviation theory, we determine the fine structure in the probability distribution of the observable displacement of a bead coupled to a molecular motor. More generally, for any stochastic motion along a periodic substrate, this approach reveals a discrete symmetry of this distribution for which hidden degrees of freedom lead to a periodic modulation of the slope typically associated with the fluctuation theorem. Contrary to previous interpretations of experimental data, the mean force exerted by a molecular motor is unrelated to the long-tim…
Three problems in the statistical mechanics of models for an assembly of molecular motors interacting with cytoskeletal filaments are reviewed. First, a description of the hydrodynamical behaviour of density-density correlations in fluctuating ratchet models for interacting molecular motors is outlined. Numerical evidence indicates that the scaling properties of dynamical behavior in such models belong to the KPZ universality class. Second, the generalization of such models to include boundary injection and removal of motors is provided. In common with known results for the asymmetric exclusio…
In this paper we investigate the use of path-integral formalism and the concepts of entropy and traffic in the context of molecular motors. We show that together with time-reversal symmetry breaking arguments one can find bounds on efficiencies of such motors. To clarify this techinque we use it on one specific model to find both the thermodynamic and the Stokes efficiencies, although the arguments themselves are more general and can be used on a wide class of models. We also show that by considering the molecular motor as a ratchet, one can find additional bounds on the thermodynamic efficien…
Particles moving in oscillating potential with broken mirror symmetry are considered. We calculate their energetic efficiency, when acting as molecular motors carrying a load against external force. It is shown that interaction between particles enhances the efficiency in wide range of parameters. Possible consequences for artificial molecular motors are discussed.
Many single molecule experiments for molecular motors comprise not only the motor but also large probe particles coupled to it. The theoretical analysis of these assays, however, often takes into account only the degrees of freedom representing the motor. We present a coarse-graining method that maps a model comprising two coupled degrees of freedom which represent motor and probe particle to such an effective one-particle model by eliminating the dynamics of the probe particle in a thermodynamically and dynamically consistent way. The coarse-grained rates obey a local detailed balance conditi…
We model a processive linear molecular motor as a particle diffusing in a one-dimensional periodic lattice with arbitrary transition rates between its sites. We present a relatively simple proof of a theorem which states that the ratio of the drift velocity V to the diffusion coefficient D has the upper bound 2N/d, where N is the number of nodes in an elementary cell and d denotes its length. This relation can be used to estimate the minimal value of internal states of the motor and the maximal value of the so called Einstein force, which approximately equals to the maximal force exerted by a …
The diffusion of a molecular motor in the presence of a constant external force is considered on the basis of a simple theoretical model. The motor is represented by a Brownian particle moving in a series of parabolic potentials placed periodically on a line, and the potential is switched stochastically from one parabola to another by a chemical reaction, which corresponds to the ATP hydrolysis or synthesis in motor proteins. It is found that the diffusion coefficient as a function of the force exhibits peaks. The mechanism of this diffusion enhancement and the possibility of observing it in F…
Molecular motors convert chemical energy into mechanical work while operating in an environment dominated by Brownian motion. The aim of this paper is to explore the flow of energy between the molecular motors and its surroundings, in particular, its efficiency. Based on the Fokker-Planck equation with either $N$ or infinite chemical states, we find that the energy efficiency of the molecular motors, whether the Stokes efficiency or the usual thermodynamic efficiency, is strictly bounded by 1, because of the dissipation of the energy in both the overdamped surroundings and in the process of th…
Molecular motors transport various cargos along cytoskeletal filaments, analogous to trucks on roads. In contrast to vehicles, however, molecular motors do not work alone but in small teams. We describe a simple model for the transport of a cargo by one team of motors and by two teams of motors, which walk into opposite directions. The cooperation of one team of motors generates long-range transport, which we observed experimentally in vitro. Transport by two teams of motors leads to a variety of bidirectional motility behaviour and to dynamic instabilities reminiscent of spontaneous symmetry …
We introduce a general framework to study the processivity of molecular motors moving along a polar filament and discuss the average time spent attached to the filament as a function of a tangentially applied load. Our study of specific models suggests that the attachment time of a motor decreases with increasing ATP concentration and that double-headed motors such as kinesins lose their processivity under forcing conditions while processive single-headed motors are less sensitive to tangential forcing.
Dynamics of molecular motors that move along linear lattices and interact with them via reversible destruction of specific lattice bonds is investigated theoretically by analyzing exactly solvable discrete-state ``burnt-bridge'' models. Molecular motors are viewed as diffusing particles that can asymmetrically break or rebuild periodically distributed weak links when passing over them. Our explicit calculations of dynamic properties show that coupling the transport of the unbiased molecular motor with the bridge-burning mechanism leads to a directed motion that lowers fluctuations and produces…
The traffic of molecular motors through open tube-like compartments is studied using lattice models. These models exhibit boundary-induced phase transitions related to those of the asymmetric simple exclusion process (ASEP) in one dimension. The location of the transition lines depends on the boundary conditions at the two ends of the tubes. Three types of boundary conditions are studied: (A) Periodic boundary conditions which correspond to a closed torus-like tube. (B) Fixed motor densities at the two tube ends where radial equilibrium holds locally; and (C) Diffusive motor injection at one e…
We study the mechanical and thermodynamic properties of different traffic models for kinesin which are relevant in biological and experimental contexts. We find that motor-motor interactions play a fundamental role by enhancing the thermodynamic efficiency at maximum power of the motors, as compared to the non-interacting system, in a wide range of biologically compatible scenarios. We furthermore consider the case where the motor-motor interaction directly affects the internal chemical cycle and investigate the effect on the system dynamics and thermodynamics.
In a single molecule assay, the motion of a molecular motor is often inferred from measuring the stochastic trajectory of a large probe particle attached to it. We discuss a simple model for this generic set-up taking into account explicitly the elastic coupling between probe and motor. The combined dynamics consists of discrete steps of the motor and continuous Brownian motion of the probe. Motivated by recent experiments on the F1-ATPase, we investigate three types of efficiencies both in simulations and a Gaussian approximation. Overall, we obtain good quantitative agreement with the experi…
Most computer simulations of molecular dynamics take place under equilibrium conditions--in a closed, isolated system, or perhaps one held at constant temperature or pressure. Sometimes, extra tensions, shears, or temperature gradients are introduced to those simulations to probe one type of nonequilibrium response to external forces. Catalysts and molecular motors, however, function based on the nonequilibrium dynamics induced by a chemical reaction's thermodynamic driving force. In this scenario, simulations require chemostats capable of preserving the chemical concentrations of the nonequil…
We present a quantitative analysis of recent data on the kinetics of ATP hydrolysis, which has presented a puzzle regarding the load dependence of the Michaelis constant. Within the framework of coarse grained two-state ratchet models, our analysis not only explains the puzzling data, but provides a modified Michaelis law, which could be useful as a guide for future experiments.
We have developed a novel method to evaluate the potential profile of a molecular motor at each chemical state from only the probe's trajectory and applied it to a rotary molecular motor F$_1$-ATPase. By using this method, we could also obtain the information regarding the mechanochemical coupling and energetics. We demonstrate that the position-dependent transition of the chemical states is the key feature for the highly efficient free-energy transduction by F$_1$-ATPase.
Theoretical analysis, which maps single molecule time trajectories of a molecular motor onto unicyclic Markov processes, allows us to evaluate the heat dissipated from the motor and to elucidate its dependence on the mean velocity and diffusivity. Unlike passive Brownian particles in equilibrium, the velocity and diffusion constant of molecular motors are closely inter-related to each other. In particular, our study makes it clear that the increase of diffusivity with the heat production is a natural outcome of active particles, which is reminiscent of the recent experimental premise that the …
Molecular motors do not work in isolation {\it in-vivo}. We highlight some of the coordinations, cooperations and competitions that determine the collective properties of molecular motors in eukaryotic cells. In the context of traffic-like movement of motors on a track, we emphasize the importance of single-motor bio-chemical cycle and enzymatic activity on their collective spatio-temporal organisation. Our modelling strategy is based on a synthesis- the same model describes the single-motor mechano-chemistry at sufficiently low densities whereas at higher densities it accounts for the collect…
Movements of molecular motors on cytoskeletal filaments are described by directed walks on a line. Detachment from this line is allowed to occur with a small probability. Motion in the surrounding fluid is described by symmetric random walks. Effects of detachment and reattachment are calculated by an analytical solution of the master equation. Results are obtained for the fraction of bound motors, their average velocity and displacement. Enclosing the system in a finite geometry (tube, slab) leads to an experimentally realizable problem, that is studied in a continuum description and also num…
Processive molecular motors which drive the traffic of organelles in cells move in a directed way along cytoskeletal filaments. On large time scales, they perform motor walks, i.e., peculiar random walks which arise from the repeated unbinding from and rebinding to filaments. Unbound motors perform Brownian motion in the surrounding fluid. In addition, the traffic of molecular motors exhibits many cooperative phenomena. In particular, it faces similar problems as the traffic on streets such as the occurrence of traffic jams and the coordination of (two-way) traffic. These issues are studied he…
Properties of transport of molecular motors are investigated. A simplified model based on the concept of Brownian ratchets is applied. We analyze a stochastic equation of motion by means of numerical methods. The transport is systematically studied with respect to its energetic efficiency and quality expressed by an effective diffusion coefficient. We demonstrate the role of friction and non-equilibrium driving on the transport quantifiers and identify regions of a parameter space where motors are optimally transported.
The stationary states of systems with many molecular motors are studied theoretically for uniaxial and centered (aster-like) arrangements of cytoskeletal filaments using Monte Carlo simulations and a two-state model. Mutual exclusion of motors from binding sites of the filaments is taken into account. For small overall motor concentration, the density profiles are exponential and algebraic in uniaxial and centered filament systems, respectively. For uniaxial systems, exclusion leads to the coexistence of regions of high and low densities of bound motors corresponding to motor traffic jams, whi…
We model the dynamics of a processive or rotary molecular motor using a renewal processes, in line with the work initiated by Svoboda, Mitra and Block. We apply a functional technique to compute different types of multiple-time correlation functions of the renewal process, which have applications to bead-assay experiments performed both with processive molecular motors, such as myosin V and kinesin, and rotary motors, such as F1-ATPase.
Molecular motors convert chemical energy derived from the hydrolysis of ATP into mechanical energy. A well-studied model of a molecular motor is the flashing ratchet model. We show that this model exhibits a fluctuation relation known as the Gallavotti-Cohen symmetry. Our study highlights the fact that the symmetry is present only if the chemical and mechanical degrees of freedom are both included in the description.
We present a theoretical framework to understand a modified fluctuation-dissipation theorem valid for systems close to non-equilibrium steady-states and obeying markovian dynamics. We discuss the interpretation of this result in terms of trajectory entropy excess. The framework is illustrated on a simple pedagogical example of a molecular motor. We also derive in this context generalized Green-Kubo relations similar to the ones derived recently by Seifert., Phys. Rev. Lett., 104, 138101 (2010) for more general networks of biomolecular states.
The extraction of membrane tubes by molecular motors is known to play an important role for the transport properties of eukaryotic cells. By studying a generic class of models for the tube extraction, we discover a rich phase diagram. In particular we show that the density of motors along the tube can exhibit shocks, inverse shocks and plateaux, depending on parameters which could in principle be probed experimentally. In addition the phase diagram exhibits interesting reentrant behavior.
We discuss the force-velocity relations obtained in a two-state crossbridge model for molecular motors. They can be calculated analytically in two limiting cases: for a large number and for one pair of motors. The effect of the strain-dependent detachment rate on the motor characteristics is studied. It can lead to linear, myosin-like, kinesin-like and anomalous curves. In particular, we specify the conditions under which oscillatory behavior may be found.
For a single enzyme or molecular motor operating in an aqueous solution of non-equilibrated solute concentrations, a thermodynamic description is developed on the level of an individual trajectory of transitions between states. The concept of internal energy, intrinsic entropy and free energy for states follows from a microscopic description using one assumption on time-scale separation. A first law energy balance then allows the unique identification of the heat dissipated in one transition. Consistency with the second law on the ensemble level enforces both stochastic entropy as third contri…
The traffic of molecular motors which interact through mutual exclusion is studied theoretically for half-open tube-like compartments. These half-open tubes mimic the shapes of axons. The mutual exclusion leads to traffic jams or density plateaus on the filaments. A phase transition is obtained when the motor velocity changes sign. We identify the relevant length scales and characterize the jamming behavior using both analytical approximations and Monte Carlo simulations of lattice models.
A model of an autonomous isothermal Brownian motor with an internal propulsion mechanism is considered. The motor is a Brownian particle which is semi-transparent for molecules of surrounding ideal gas. Molecular passage through the particle is controlled by a potential similar to that in the transition rate theory, i.e. characterized by two stationary states with a finite energy difference separated by a potential barrier. The internal potential drop maintains the diode-like asymmetry of molecular fluxes through the particle, which results in the particle's stationary drift.
We propose a two-dimensional model for the organization of stabilized microtubules driven by molecular motors in an unconfined geometry. In this model two kinds of dynamics are competing. The first one is purely diffusive, with an interaction between the rotational degrees of freedom, the second one is a local drive, dependent on microtubule polarity. As a result, there is a configuration dependent driving field. Applying a molecular field approximation, we are able to derive continuum equations. A study on the solutions shows nonequilibrium steady states. The presence and stability of such se…
Enzymatic molecules that actively support many cellular processes, including transport, cell division and cell motility, are known as motor proteins or molecular motors. Experimental studies indicate that they interact with each other and they frequently work together in large groups. To understand the mechanisms of collective behavior of motor proteins we study the effect of interactions in the transport of molecular motors along linear filaments. It is done by analyzing a recently introduced class of totally asymmetric exclusion processes that takes into account the intermolecular interactio…
We discuss effects of the stepping kinetics of molecular motors on their traffic behavior on crowded filaments using a simple two-state chemomechanical cycle. While the general traffic behavior is quite robust with respect to the detailed kinetics of the step, a few observable parameters exhibit a strong dependence on these parameters. Most strikingly, the effective unbinding rate of the motors may both increase and decrease with increasing traffic density, depending on the details of the motor step. Likewise the run length either exhibits a strong decrease or almost no dependence on the traff…
Dynamics of molecular motor dimers, consisting of rigidly bound particles that move along two parallel lattices and interact with underlying molecular tracks, is investigated theoretically by analyzing discrete-state stochastic continuous-time burnt-bridge models. In these models the motion of molecular motors is viewed as a random walk along the lattices with periodically distributed weak links (bridges). When the particle crosses the weak link it can be destroyed with a probability $p$, driving the molecular motor motion in one direction. Dynamic properties and effective generated forces of …
Systems with two species of active molecular motors moving on (cytoskeletal) filaments into opposite directions are studied theoretically using driven lattice gas models. The motors can unbind from and rebind to the filaments. Two motors are more likely to bind on adjacent filament sites if they belong to the same species. These systems exhibit (i) Continuous phase transitions towards states with spontaneously broken symmetry, where one motor species is largely excluded from the filament, (ii) Hysteresis of the total current upon varying the relative concentrations of the two motor species, an…
Molecular motors interacting with cytoskeletal filaments undergo peculiar random walks consisting of alternating sequences of directed movements along the filaments and diffusive motion in the surrounding solution. An ensemble of motors is studied which interacts with a single filament in two and three dimensions. The time evolution of the probability distribution for the bound and unbound motors is determined analytically. The diffusion of the motors is strongly enhanced parallel to the filament. The analytical expressions are in excellent agreement with the results of Monte Carlo simulations…
A simple tight-coupling model of a molecular chemical engine is proposed. The efficiency of the chemical engine and its average velocity can be explicitly calculated. The diffusion constant is evaluated approximately using the fluctuation theorem. Langevin simulations with stochastic boundary conditions are performed and the numerical results are compared with theoretical calculations.
The energetics and efficiency of a linear molecular motor model proposed by Mogilner et al. (Phys. Lett. 237, 297 (1998)) is analyzed from an analytical point of view. The model which is based on protein friction with a track is described by coupled Langevin equations for the motion in combination with coupled master equations for the ATP hydrolysis. Here the energetics and efficiency of the motor is addressed using a many body scheme with focus on the efficiency at maximum power (EMP). It is found that the EMP is reduced from about 10 pct in a heuristic description of the motor to about 1 per…
We examine the dependence of the physical quantities of the rotatory molecular motor, such as the rotation velocity and the proton translocation rate, on the chemical reaction rate using the model based only on diffusion process. A peculiar behavior of proton translocation is found and the energy transduction efficiency of the motor protein is enhanced by this behavior. We give a natural explanation that this behavior is universal when certain inequalities between chemical reaction rates hold. That may give a clue to examine whether the motion of the molecular motor is dominated by diffusion p…
This review is focused on the application of specific fluctuation relations, such as the Gallavotti-Cohen relation, to ratchet models of a molecular motor. A special emphasis is placed on two-states models such as the flashing ratchet model. We derive the Gallavotti-Cohen fluctuation relation for these models and we discuss some of its implications.
An elegant formula for coordinates of carbon atoms in a unit cell of a single-walled nanotube (SWNT) is presented and a new molecular motor of double-walled carbon nanotube whose inner tube is a long (8,4) SWNT and outer tube a short (14,8) SWNT is constructed. The interaction between inner an outer tubes is analytically derived by summing the Lennard-Jones potentials between atoms in inner and outer tubes. It is proved that the molecular motor in a thermal bath exhibits a directional motion with the temperature variation of the bath.
Molecular motors belonging to the kinesin and myosin super family hydrolyze ATP by cycling through a sequence of chemical states. These cytoplasmic motors are dimers made up of two linked identical monomeric globular proteins. Fueled by the free energy generated by ATP hydrolysis, the motors walk on polar tracks (microtubule or filamentous actin) processively, which means that only one head detaches and executes a mechanical step while the other stays bound to the track. Thus, the one motor head must regulate chemical state of the other, referred to as "gating", a concept that is not fully und…
Molecular motors perform active movements along cytoskeletal filaments and drive the traffic of organelles and other cargo particles in cells. In contrast to the macroscopic traffic of cars, however, the traffic of molecular motors is characterized by a finite walking distance (or run length) after which a motor unbinds from the filament along which it moves. Unbound motors perform Brownian motion in the surrounding aqueous solution until they rebind to a filament. We use variants of driven lattice gas models to describe the interplay of their active movements, the unbound diffusion, and the b…
A molecular motor is made of either a single macromolecule or a macromolecular complex. Just like their macroscopic counterparts, molecular motors "transduce" input energy into mechanical work. All the nano-motors considered here operate under isothermal conditions far from equilibrium. Moreover, one of the possible mechanisms of energy transduction, called Brownian ratchet, does not even have any macroscopic counterpart. But, molecular motor is not synonymous with Brownian ratchet; a large number of molecular motors execute a noisy power stroke, rather than operating as Brownian ratchet. We r…
Dynamic properties of molecular motors whose motion is powered by interactions with specific lattice bonds are studied theoretically with the help of discrete-state stochastic "burnt-bridge" models. Molecular motors are depicted as random walkers that can destroy or rebuild periodically distributed weak connections ("bridges") when crossing them, with probabilities $p_1$ and $p_2$ correspondingly. Dynamic properties, such as velocities and dispersions, are obtained in exact and explicit form for arbitrary values of parameters $p_1$ and $p_2$. For the unbiased random walker, reversible burning …
The transport of cargo particles which are pulled by several molecular motors in a cooperative manner is studied theoretically. The transport properties depend primarily on the maximal number, $N$, of motor molecules that may pull simultaneously on the cargo particle. Since each motor must unbind from the filament after a finite number of steps but can also rebind to it again, the actual number of pulling motors is not constant but varies with time between zero and $N$. An increase in the maximal number $N$ leads to a strong increase of the average walking distance (or run length) of the cargo…
A hopping model for molecular motors is presented consisting of a state with asymmetric hopping rates with period 2 and a state with uniform hopping rates. State changes lead to a stationary unidirectional current of a particle. The current is explicitly calculated as a function of the rate of state changes, including also an external bias field. The Einstein relation between the linear mobility of the particle and its diffusion coefficient is investigated. The power input into the system is derived, as well as the power output resulting from the work performed against the bias field. The effi…
The statistics of steps and dwell times in reversible molecular motors differ from those of cycle completion in enzyme kinetics. The reason is that a step is only one of several transitions in the mechanochemical cycle. As a result, theoretical results for cycle completion in enzyme kinetics do not apply to stepping data. To allow correct parameter estimation, and to guide data analysis and experiment design, a theoretical treatment is needed that takes this observation into account. In this paper, we model the distribution of dwell times and number of forward and backward steps using first pa…
Linear bio-molecular motors move unidirectionally along a track by coordinating several different processes, such as fuel (ATP) capture, hydrolysis, conformational changes, binding and unbinding from a track, and center-of-mass diffusion. A better understanding of the interdependencies between these processes, which take place over a wide range of different time scales, would help elucidate the general operational principles of molecular motors. Artificial molecular motors present a unique opportunity for such a study because motor structure and function are a priori known. Here we describe us…
