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Debashish Chowdhury

Publications and source records attributed to Debashish Chowdhury.

At least 73 records · Page 4Linked to original sources

Traffic of single-headed motor proteins KIF1A: effects of lane changing

KIF1A kinesins are single-headed motor proteins which move on cylindrical nano-tubes called microtubules (MT). A normal MT consists of 13 protofilaments on which the equispaced motor binding sites form a periodic array. The collective movement of the kinesins on a MT is, therefore, analogous to vehicular traffic on multi-lane highways where each protofilament is the analogue of a single lane. Does lane-changing increase or decrease the motor flux per lane? We address this fundamental question here by appropriately extending a recent model [{\it Phys. Rev. E {\bf 75}, 041905 (2007)}]. By carrying out analytical calculations and computer simulations of this extended model, we predict that the flux per lane can increase or decrease with the increasing rate of lane changing, depending on the concentrations of motors and the rate of hydrolysis of ATP, the ``fuel'' molecules. Our predictions can be tested, in principle, by carrying out {\it in-vitro} experiments with fluorescently labelled KIF1A molecules.

physics.bio-ph↗

Traffic phenomena in biology: from molecular motors to organisms

Traffic-like collective movements are observed at almost all levels of biological systems. Molecular motor proteins like, for example, kinesin and dynein, which are the vehicles of almost all intra-cellular transport in eukayotic cells, sometimes encounter traffic jam that manifests as a disease of the organism. Similarly, traffic jam of collagenase MMP-1, which moves on the collagen fibrils of the extracellular matrix of vertebrates, has also been observed in recent experiments. Traffic-like movements of social insects like ants and termites on trails are, perhaps, more familiar in our everyday life. Experimental, theoretical and computational investigations in the last few years have led to a deeper understanding of the generic or common physical principles involved in these phenomena. In particular, some of the methods of non-equilibrium statistical mechanics, pioneered almost a hundred years ago by Einstein, Langevin and others, turned out to be powerful theoretical tools for quantitative analysis of models of these traffic-like collective phenomena as these systems are intrinsically far from equilibrium. In this review we critically examine the current status of our understanding, expose the limitations of the existing methods, mention open challenging questions and speculate on the possible future directions of research in this interdisciplinary area where physics meets not only chemistry and biology but also (nano-)technology.

physics.bio-ph↗

Intra-cellular traffic: bio-molecular motors on filamentary tracks

Molecular motors are macromolecular complexes which use some form of input energy to perform mechanical work. The filamentary tracks, on which these motors move, are made of either proteins (e.g., microtubules) or nucleic acids (DNA or RNA). Often, many such motors move simultaneously on the same track and their collective properties have superficial similarities with vehicular traffic on highways. The models we have developed provide ``unified'' description: in the low-density limit, a model captures the transport properties of a single motor while, at higher densities the same model accounts for the collective spatio-temporal organization of interacting motors. By drawing analogy with vehicular traffic, we have introduced novel quantities for characterizing the nature of the spatio-temporal organization of molecular motors on their tracks. We show how the traffic-like intracellular collective phenomena depend on the mechano-chemistry of the corresponding individual motors.

physics.bio-ph↗

Interacting RNA polymerase motors on DNA track: effects of traffic congestion and intrinsic noise on RNA synthesis

RNA polymerase (RNAP) is an enzyme that synthesizes a messenger RNA (mRNA) strand which is complementary to a single-stranded DNA template. From the perspective of physicists, an RNAP is a molecular motor that utilizes chemical energy input to move along the track formed by a DNA. In many circumstances, which are described in this paper, a large number of RNAPs move simultaneously along the same track; we refer to such collective movements of the RNAPs as RNAP traffic. Here we develop a theoretical model for RNAP traffic by incorporating the steric interactions between RNAPs as well as the mechano-chemical cycle of individual RNAPs during the elongation of the mRNA. By a combination of analytical and numerical techniques, we calculate the rates of mRNA synthesis and the average density profile of the RNAPs on the DNA track. We also introduce, and compute, two new measures of fluctuations in the synthesis of RNA. Analyzing these fluctuations, we show how the level of {\it intrinsic noise} in mRNA synthesis depends on the concentrations of the RNAPs as well as on those of some of the reactants and the products of the enzymatic reactions catalyzed by RNAP. We suggest appropriate experimental systems and techniques for testing our theoretical predictions.

physics.bio-ph↗

Molecular motors: design, mechanism and control

Biological functions in each animal cell depend on coordinated operations of a wide variety of molecular motors. Some of the these motors transport cargo to their respective destinations whereas some others are mobile workshops which synthesize macromolecules while moving on their tracks. Some other motors are designed to function as packers and movers. All these motors require input energy for performing their mechanical works and operate under conditions far from thermodynamic equilibrium. The typical size of these motors and the forces they generate are of the order of nano-meters and pico-Newtons, respectively. They are subjected to random bombardments by the molecules of the surrounding aqueous medium and, therefore, follow noisy trajectories. Because of their small inertia, their movements in the viscous intracellular space exhibits features that are characteristics of hydrodynamics at low Reynold's number. In this article we discuss how theoretical modeling and computer simulations of these machines by physicists are providing insight into their mechanisms which engineers can exploit to design and control artificial nano-motors.

physics.bio-ph↗

RNA polymerase motors on DNA track: effects of traffic congestion on RNA synthesis

RNA polymerase (RNAP) is an enzyme that synthesizes a messenger RNA (mRNA) strand which is complementary to a single-stranded DNA template. From the perspective of physicists, an RNAP is a molecular motor that utilizes chemical energy input to move along the track formed by a ssDNA. In some circumstances, which are described in this paper, a large number of RNAPs move simultaneously along the same track. We refer to such collective movements of the RNAPs as RNAP traffic because of the similarities between the collective dynamics of the RNAPs on ssDNA track and that of vehicles in highway traffic. In this paper we develop a theoretical model for RNAP traffic by incorporating the steric interactions between RNAPs as well as the mechano-chemical cycle of individual RNAPs during the elongation of the mRNA. By a combination of analytical and numerical techniques, we calculate the rates of mRNA synthesis and the average density profile of the RNAPs on the ssDNA track. We also suggest novel experiments for testing our theoretical predictions.

physics.bio-ph↗

Modeling protein synthesis from a physicist's perspective: a toy model

Proteins are polymers of amino acids. These macromolecules are synthesized by intracellular machines called ribosomes. Although the experimental investigation of protein synthesis has been a traditional area of research in molecular cell biology, important quantitative models of protein synthesis have been reported in research journals devoted to statistical physics and related interdisciplinary topics. From the perspective of a physicist, protein synthesis is the classical transport of interacting ribosomes on a messenger RNA (mRNA) template that dictates the sequence of the amino acids on the protein. We discuss appropriate simplification of the models and methods. In particular, we develop and analyze a simple toy model using some elementary techniques of non-equilibrium statistical mechanics and predict the average rate of protein synthesis and the spatial organization of the ribosomes in the steady state.

physics.bio-ph↗

Modelling of self-driven particles: foraging ants and pedestrians

Models for the behavior of ants and pedestrians are studied in an unified way in this paper. Each ant follows pheromone put by preceding ants, hence creating a trail on the ground, while pedestrians also try to follow others in a crowd for efficient and safe walking. These following behaviors are incorporated in our stochastic models by using only local update rules for computational efficiency. It is demonstrated that the ant trail model shows an unusual non-monotonic dependence of the average speed of the ants on their density, which can be well analyzed by the zero-range process. We also show that this anomalous behavior is clearly observed in an experiment of multiple robots. Next, the relation between the ant trail model and the floor field model for studying evacuation dynamics of pedestrians is discussed. The latter is regarded as a two-dimensional generalization of the ant trail model, where the pheromone is replaced by footprints.

cond-mat.stat-mech↗

Dynamic instability of microtubules: effect of catastrophe-suppressing drugs

Microtubules are stiff filamentary proteins that constitute an important component of the cytoskeleton of cells. These are known to exhibit a dynamic instability. A steadily growing microtubule can suddenly start depolymerizing very rapidly; this phenomenon is known as ``catastrophe''. However, often a shrinking microtubule is ``rescued'' and starts polymerizing again. Here we develope a model for the polymerization-depolymerization dynamics of microtubules in the presence of {\it catastrophe-suppressing drugs}. Solving the dynamical equations in the steady-state, we derive exact analytical expressions for the length distributions of the microtubules tipped with drug-bound tubulin subunits as well as those of the microtubules, in the growing and shrinking phases, tipped with drug-free pure tubulin subunits. We also examine the stability of the steady-state solutions.

cond-mat.stat-mech↗

Physics of Transport and Traffic Phenomena in Biology: from molecular motors and cells to organisms

Traffic-like collective movements are observed at almost all levels of biological systems. Molecular motor proteins like, for example, kinesin and dynein, which are the vehicles of almost all intra-cellular transport in eukayotic cells, sometimes encounter traffic jam that manifests as a disease of the organism. Similarly, traffic jam of collagenase MMP-1, which moves on the collagen fibrils of the extracellular matrix of vertebrates, has also been observed in recent experiments. Traffic-like movements of social insects like ants and termites on trails are, perhaps, more familiar in our everyday life. Experimental, theoretical and computational investigations in the last few years have led to a deeper understanding of the generic or common physical principles involved in these phenomena. In particular, some of the methods of non-equilibrium statistical mechanics, pioneered almost a hundred years ago by Einstein, Langevin and others, turned out to be powerful theoretical tools for quantitaive analysis of models of these traffic-like collective phenomena as these systems are intrinsically far from equilibrium. In this review we critically examine the current status of our understanding, expose the limitations of the existing methods, mention open challenging questions and speculate on the possible future directions of research in this interdisciplinary area where physics meets not only chemistry and biology but also (nano-)technology.

physics.bio-ph↗

Alice in a micro-factory: modeling materials and mechanisms of natural nano-machines

Imagine an under water factory which is about $10 μ$m long in each direction. The factory is filled with machines, each typically a few tens of nanometers long, which perform specfic tasks and operate in a well coordinated manner. A cell, the structural and functional unit of life, is not very different from this micro-factory. In this article, I begin with Alice's guided tour of this micro-factory in her dream during which the guide shows her wide varieties of the nano-machines in this factory. The style of presentation of the first half of this article is inspired by Lewis Carrol's {\it Alice in Wonderland}. In the second half, I introduce the methods of studying the materials and mechanisms of the molecular machines through dialogues; the three participants in this discussion are Alice, her elder brother Alex and her father Albert. The style of presentation of the second half of this article, in terms of a dialogue, is adapted from Galileo's {\it Dialogue Concerning the Two Chief World Systems}. Albert, a professor of biophysics, emphasizes the crucial differences between the mechanisms of the natural nano-machines and those of their macroscopic counterparts. He also points out some practical applications of this interdisciplinary research in biomedical science and nano-technology.

physics.bio-ph↗

Intra-cellular transport by single-headed kinesin KIF1A: effects of single-motor mechano-chemistry and steric interactions

In eukaryotic cells, many motor proteins can move simultaneously on a single microtubule track. This leads to interesting collective phenomena like jamming. Recently we reported ({\it Phys. Rev. Lett. {\bf 95}, 118101 (2005)}) a lattice-gas model which describes traffic of unconventional (single-headed) kinesins KIF1A. Here we generalize this model, introducing a novel interaction parameter $c$, to account for an interesting mechano-chemical process which has not been considered in any earlier model. We have been able to extract all the parameters of the model, except $c$, from experimentally measured quantities. In contrast to earlier models of intra-cellular molecular motor traffic, our model assigns distinct ``chemical'' (or, conformational) states to each kinesin to account for the hydrolysis of ATP, the chemical fuel of the motor. Our model makes experimentally testable theoretical predictions. We determine the phase diagram of the model in planes spanned by experimentally controllable parameters, namely, the concentrations of kinesins and ATP. Furthermore, the phase-separated regime is studied in some detail using analytical methods and simulations to determine e.g. the position of shocks. Comparison of our theoretical predictions with experimental results is expected to elucidate the nature of the mechano-chemical process captured by the parameter $c$.

physics.bio-ph↗

From aggressive driving to molecular motor traffic

Motivated by recent experimental results for the step sizes of dynein motor proteins, we develope a cellular automata model for intra-cellular traffic of dynein motors incorporating special features of the hindrance-dependent step size of the individual motors. We begin by investigating the properties of the aggressive driving model (ADM), a simple cellular automata-based model of vehicular traffic, a unique feature of which is that it allows a natural extension to capture the essential features of dynein motor traffic. We first calculate several collective properties of the ADM, under both periodic and open boundary conditions, analytically using two different mean-field approaches as well as by carrying out computer simulations. Then we extend the ADM by incorporating the possibilities of attachment and detachment of motors on the track which is a common feature of a large class of motor proteins that are collectively referred to as cytoskeletal motors. The interplay of the boundary and bulk dynamics of attachment and detachment of the motors to the track gives rise a phase where high and low density phases separated by a stable domain wall coexist. We also compare and contrast our results with the model of Parmeggiani et. al. (Phys. Rev. Lett. {\bf 90}, 086601 (2003)) which can be regarded as a minimal model for traffic of a closely related family of motor proteins called kinesin. Finally, we compare the transportation efficiencies of dynein and kinesin motors over a range of values of the model parameters.

cond-mat.stat-mech↗

Competition of coarsening and shredding of clusters in a driven diffusive lattice gas

We investigate a driven diffusive lattice gas model with two oppositely moving species of particles. The model is motivated by bi-directional traffic of ants on a pre-existing trail. A third species, corresponding to pheromones used by the ants for communication, is not conserved and mediates interactions between the particles. Here we study the spatio-temporal organization of the particles. In the uni-directional variant of this model it is known to be determined by the formation and coarsening of ``loose clusters''. For our bi-directional model, we show that the interaction of oppositely moving clusters is essential. In the late stages of evolution the cluster size oscillates because of a competition between their `shredding' during encounters with oppositely moving counterparts and subsequent "coarsening" during collision-free evolution. We also establish a nontrivial dependence of the spatio-temporal organization on the system size.

physics.bio-ph↗

Collective effects in intra-cellular molecular motor transport: coordination, cooperation and competetion

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 collective flow properties and the density profiles of the motors. We consider two specific examples, namely, traffic of single-headed kinesin motors KIF1A on a microtubule track and ribosome traffic on a messenger RNA track.

physics.bio-ph↗

Traffic of interacting ribosomes: effects of single-machine mechano-chemistry on protein synthesis

Many ribosomes simultaneously move on the same messenger RNA (mRNA), each separately synthesizing the protein coded by the mRNA. Earlier models of ribosome traffic represent each ribosome by a ``self-propelled particle'' and capture the dynamics by an extension of the totally asymmetric simple exclusion process (TASEP). In contrast, here we develope a theoretical model that not only incorporates the mutual exclusions of the interacting ribosomes, but also describes explicitly the mechano-chemistry of each of these individual cyclic machines during protein synthesis. Using analytical and numerical techniques of non-equilibrium statistical mechanics, we analyze this model and illustrate its power by making experimentally testable predictions on the rate of protein synthesis in real time and the density profile of the ribosomes on some mRNAs in E-Coli.

physics.bio-ph↗

Intra-cellular transport of single-headed molecular motors KIF1A

Motivated by experiments on single-headed kinesin KIF1A, we develop a model of intra-cellular transport by interacting molecular motors. It captures explicitly not only the effects of ATP hydrolysis, but also the ratchet mechanism which drives individual motors. Our model accounts for the experimentally observed single molecule properties in the low density limit and also predicts a phase diagram that shows the influence of hydrolysis and Langmuir kinetics on the collective spatio-temporal organization of the motors. Finally, we provide experimental evidence for the existence of domain walls in our {\it in-vitro} experiment with fluorescently labeled KIF1A.

physics.bio-ph↗

100 years of Einstein's theory of Brownian motion: from pollen grains to protein trains

Experimental verification of the theoretical predictions made by Albert Einstein in his paper, published in 1905, on the molecular mechanisms of Brownian motion established the existence of atoms. In the last 100 years discoveries of many facets of the ubiquitous Brownian motion has revolutionized our fundamental understanding of the role of {\it thermal fluctuations} in the exotic structures and complex dynamics exhibited by soft matter like, for example, colloids, gels, etc. The domain of Brownian motion transcends the traditional disciplinary boundaries of physics and has become an area of multi-disciplinary research. Brownian motion finds applications also in earth and environmental sciences as well as life sciences. Nature exploits Brownian motion for running many dynamical processes that are crucial for sustaining life. In the first one-third of this article I present a brief historical survey of the initial period, including works of Brown and Einstein. In the next one-third I introduce the main concepts and the essential theoretical techniques used for studying translational as well as rotational Brownian motions and the effects of time-independent potentials. In the last one-third of this article I discuss some contemporary problems on Brownian motion in time-dependent potentials, namely, {\it stochastic resonance} and {\it Brownian ratchet}, two of the hottest topics in this area of interdisciplinary research.

cond-mat.stat-mech↗