SearcharxivSearch

arXiv subjects

Debashish Chowdhury

Publications and source records attributed to Debashish Chowdhury.

At least 19 recordsLinked to original sources

Physics of collective transport and traffic phenomena in biology: progress in 20 years

Enormous progress have been made in the last 20 years since the publication of our review \cite{csk05polrev} in this journal on transport and traffic phenomena in biology. In this brief article we present a glimpse of the major advances during this period. First, we present similarities and differences between collective intracellular transport of a single micron-size cargo by multiple molecular motors and that of a cargo particle by a team of ants on the basis of the common principle of load-sharing. Second, we sketch several models all of which are biologically motivated extensions of the Asymmetric Simple Exclusion Process (ASEP); some of these models represent the traffic of molecular machines, like RNA polymerase (RNAP) and ribosome, that catalyze template-directed polymerization of RNA and proteins, respectively, whereas few other models capture the key features of the traffic of ants on trails. More specifically, using the ASEP-based models we demonstrate the effects of traffic of RNAPs and ribosomes on random and `programmed' errors in gene expression as well as on some other subcellular processes. We recall a puzzling empirical result on the single-lane traffic of predatory ants {\it Leptogenys processionalis} as well as recent attempts to account for this puzzle. We also mention some surprising effects of lane-changing rules observed in a ASEP-based model for 3-lane traffic of army ants. Finally, we explain the conceptual similarities between the pheromone-mediated indirect communication, called stigmergy, between ants on a trail and the floor-field-mediated interaction between humans in a pedestrian traffic. For the floor-field model of human pedestrian traffic we present a major theoretical result that is relevant from the perspective of all types of traffic phenomena.

physics.bio-ph

Eco-evolutionary games for harvesting self-renewing common resource: Effect of growing harvester population

The tragedy of the commons (TOC) is a ubiquitous social dilemma witnessed in interactions between a population of living entities and shared resources available to them: The individuals in the population tend to selfishly overexploit a common resource as it is arguably the rational choice, or in case of non-human beings, it may be an evolutionarily uninvadable action. How to avert the TOC is a significant problem related to the conservation of resources. It is not hard to envisage situations where the resource could be self-renewing and the size of the population may be dependent on the state of the resource through the fractions of the population employing different exploitation rates. If the self-renewal rate of the resource lies between the maximum and the minimum exploitation rates, it is not a priori obvious under what conditions the TOC can be averted. In this paper, we address this question analytically and numerically using the setup of an evolutionary game theoretical replicator equation that models the Darwinian tenet of natural selection. Through the replicator equation, while we investigate how a population of replicators exploit the shared resource, the latter's dynamical feedback on the former is also not ignored. We also present a transparent bottom-up derivation of the game-resource feedback model to facilitate future studies on the stochastic effects on the findings presented herein.

q-bio.PE

Length control of long cell protrusions: rulers, timers and transport

A living cell uses long tubular appendages for locomotion and sensory purposes. Hence, assembling and maintaining a protrusion of correct length is crucial for its survival and overall performance. Usually the protrusions lack the machinery for the synthesis of building blocks and imports them from the cell body. What are the unique features of the transport logistics which facilitate the exchange of these building blocks between the cell and the protrusion? What kind of `rulers' and `timers' does the cell use for constructing its appendages of correct length on time? How do the multiple appendages coordinate and communicate among themselves during different stages of their existence? How frequently do the fluctuations drive the length of these dynamic protrusions out of the acceptable bounds? These questions are addressed from a broad perspective in this review which is organized in three parts. In part-I the list of all known cell protrusions is followed by a comprehensive list of the mechanisms of length control of cell protrusions reported in the literature. We review not only the dynamics of the genesis of the protrusions, but also their resorption and regrowth as well as regeneration after amputation. As a case study in part-II, the specific cell protrusion that has been discussed in detail is eukaryotic flagellum (also known as cilium); this choice was dictated by the fact that flagellar length control mechanisms have been studied most extensively over more than half a century in cells with two or more flagella. Although limited in scope, brief discussions on a few non-flagellar cell protrusions in part-III of this review is intended to provide a glimpse of the uncharted territories and challenging frontiers of research on subcellular length control phenomena that awaits vigorous investigations.

physics.bio-ph

Flagellar length control in multiflagellated eukaryotes: a case study with Giardia

Every organism has a size that is convenient for its function. Not only multicellular organisms but also uni-cellular organisms and even subcellular structures have convenient sizes. Flagella of eukaryotic cells are long dynamic cell protrusions. Because of their simple linear geometry, these cell appendages have been popular system for experimental investigation of the mechanisms of size control of organelles of eukaryotic cells. In the past most of the attention have been focussed on mono-flagellates and bi-flagellates. By extending our earlier model of bi-flagellates, here we develop a theoretical model for flagellar length control in {\it Giardia} which is an octo-flagellate. It has four pairs of flagella of four different lengths. Analyzing our model we predict the different sizes of the four pairs of flagella . This analysis not only provide insight into the physical origins of the different lengths but the predicted lengths are also consistent with the experimental data.

physics.bio-ph

Game-environment feedback dynamics in growing population: Effect of finite carrying capacity

The tragedy of the commons (TOC) is an unfortunate situation where a shared resource is exhausted due to uncontrolled exploitation by the selfish individuals of a population. Recently, the paradigmatic replicator equation has been used in conjunction with a phenomenological equation for the state of the shared resource to gain insight into the influence of the games on the TOC. The replicator equation, by construction, models a fixed infinite population undergoing microevolution. Thus, it is unable to capture any effect of the population growth and the carrying capacity of the population although the TOC is expected to be dependent on the size of the population. Therefore, in this paper, we present a mathematical framework that incorporates the density dependent payoffs and the logistic growth of the population in the eco-evolutionary dynamics modelling the game-resource feedback. We discover a bistability in the dynamics: a finite carrying capacity can either avert or cause the TOC depending on the initial states of the resource and the initial fraction of cooperators. In fact, depending on the type of strategic game-theoretic interaction, a finite carrying capacity can either avert or cause the TOC when it is exactly the opposite for the corresponding case with infinite carrying capacity.

nlin.AO

Flagellar length fluctuations: quantitative dependence on length control mechanism

Organelles of optimum size are crucial for proper functioning of a living cell. The cell employs various mechanisms for actively sensing and controlling the size of its organelles. Recently Bauer et al have opened a new research frontier in the field of subcellular size control by shedding light on the noise and fluctuations of organelles of controlled size. Taking eukaryotic flagellum as a model organelle, which is quite popular for such studies because of its linear geometry and dynamic nature, Bauer et al have analysed the nature of fluctuations of its length. Here we summarize the key questions and the fundamental importance of the recent developments. Although our attention is focussed here mainly on the experimental and theoretical works on eukaryotic flagellum, the ideas are general and applicable to wide varieties of cell organelle.

physics.bio-ph

Level crossing statistics in a biologically motivated model of a long dynamic protrusion: passage times, random and extreme excursions

Long cell protrusions, which are effectively one-dimensional, are highly dynamic subcellular structures. Length of many such protrusions keep fluctuating about the mean value even in the the steady state. We develop here a stochastic model motivated by length fluctuations of a type of appendage of an eukaryotic cell called flagellum (also called cilium). Exploiting the techniques developed for the calculation of level-crossing statistics of random excursions of stochastic process, we have derived analytical expressions of passage times for hitting various thresholds, sojourn times of random excursions beyond the threshold and the extreme lengths attained during the lifetime of these model flagella. We identify different parameter regimes of this model flagellum that mimic those of the wildtype and mutants of a well known flagellated cell. By analysing our model in these different parameter regimes, we demonstrate how mutation can alter the level-crossing statistics even when the steady state length remains unaffected by the same mutation. Comparison of the theoretically predicted level crossing statistics, in addition to mean and variance of the length, in the steady state with the corresponding experimental data can be used in near future as stringent tests for the validity of the models of flagellar length control. The experimental data required for this purpose, though never reported till now, can be collected, in principle, using a method developed very recently for flagellar length fluctuations.

q-bio.SC

Decentralized decision making by an ant colony: drift-diffusion model of individual choice, quorum and collective decision

Ants are social insects. When the existing nest of an ant colony becomes uninhabitable, the hunt for a new suitable location for migration of the colony begins. Normally, multiple sites may be available as the potential new nest site. Distinct sites may be chosen by different scout ants based on their own assessments. Since the individual assessment is error prone, many ants may choose inferior site(s). But, the collective decision that emerges from the sequential and decentralized decision making process is often far better. We develop a model for this multi-stage decision making process. A stochastic drift-diffusion model (DDM) captures the sequential information accumulation by individual scout ants for arriving at their respective individual choices. The subsequent tandem runs of the scouts, whereby they recruit their active nestmates, is modelled in terms of suitable adaptations of the totally asymmetric simple exclusion processes (TASEP). By a systematic analysis of the model we explore the conditions that determine the speed of the emergence of the collective decision and the quality of that decision. More specifically, we demonstrate that collective decision of the colony is much less error-prone that the individual decisions of the scout ants. We also compare our theoretical predictions with experimental data.

nlin.AO

A pattern in the imaging data: mere artefact of spatio-temporal resolution

{\it ' Seeing is believing '} \cite{north06}- is the fundamental philosophy of optical imaging based on light microscopy \cite{ntziachristos10}. Since the pioneering works of Antonie van Leeuwenhoek and Robert Hooke in the 17th century, optical microscopy has served as one of the most important tools in biological sciences \cite{thorn16}. But interpreting visual observations with preconceived notions can potentially mislead one to erroneous conclusions.Here we report one such case where, at first sight, the interesting pattern extracted from the images of axonal transport may appear to reveal some hitherto unknown features of cargo transport driven by cytoskeletal motors \cite{ross16}. It may even be tempting to theorize about the possible molecular mechanisms that could give rise the observed pattern. But, as we conclusively demonstrate here, these patterns are mere artifacts of the spatial and temporal resolutions of imaging microscopes. These observed patterns, and their interpretations, are rather universal in the sense that in all those experiments where an observer (or machine), having limited spatial and temporal resolution, tracks the movement of classical objects moving on a one-dimensional track, such enticing patterns will invariably emerge. Our analysis here exposes pitfalls lurking in the way one interprets such patterns; unless critically analyzed, believing in whatever one is seeing, one could draw an illusory conclusion.

physics.bio-ph

Flagellar length control in monoflagellates by motorized transport: growth kinetics and correlations of length fluctuations

How does a cell self-organize so that its appendages attain specific lengths that are convenient for their respective functions? What kind of 'rulers' does a cell use to measure the length of these appendages? How does a cell transport structure building materials between the cell body and distal tips of these appendages so as to regulate their dynamic lengths during various stages of its lifetime? Some of these questions are addressed here in the context of a specific cell appendage called flagellum (also called cilium). A "time of flight" (ToF) mechanism, adapted from the pioneering idea of Galileo, has been used successfully very recently to explain the length control of flagella by a biflagellate green algae. Using the same ToF mechanism, here we develop a stochastic model for the dynamics of flagella in two different types of monoflagellate unicellular organisms. A unique feature of these monoflagellates is that these become transiently multi-flagellated during a short span of their life time. The mean length of the flagella in our model reproduce the trend of their temporal variation observed in experiments. Moreover, for probing the intracellular molecular communication between the dynamic flagella of a given cell, we have computed the correlation in the fluctuations of their lengths during the multiflagellated stage of the cell cycle by Monte Carlo simulation.

physics.bio-ph

Flagellar length control in biflagellate eukaryotes: time-of-flight, shared pool, train traffic and cooperative phenomena

Flagella of eukaryotic cells are transient long cylindrical protrusions. The proteins needed to form and maintain flagella are synthesized in the cell body and transported to the distal tips. What `rulers' or `timers' a specific type of cells use to strike a balance between the outward and inward transport of materials so as to maintain a particular length of its flagella in the steady state is one of the open questions in cellular self-organization. Even more curious is how the two flagella of biflagellates, like Chlamydomonas Reinhardtii, communicate through their base to coordinate their lengths. In this paper we develop a stochastic model for flagellar length control based on a time-of-flight (ToF) mechanism. This ToF mechanism decides whether or not structural proteins are to be loaded onto an intraflagellar transport (IFT) train just before it begins its motorized journey from the base to the tip of the flagellum. Because of the ongoing turnover, the structural proteins released from the flagellar tip are transported back to the cell body also by IFT trains. We represent the traffic of IFT trains as a totally asymmetric simple exclusion process (TASEP). The ToF mechanism for each flagellum, together with the TASEP-based description of the IFT trains, combined with a scenario of sharing of a common pool of flagellar structural proteins in biflagellates, can account for all key features of experimentally known phenomena. These include ciliogenesis, resorption, deflagellation as well as regeneration after selective amputation of one of the two flagella. We also show that the experimental observations of Ishikawa and Marshall are consistent with the ToF mechanism of length control if the effects of the mutual exclusion of the IFT trains captured by the TASEP are taken into account. Moreover, we make new predictions on the flagellar length fluctuations and the role of the common pool.

physics.bio-ph

Stochastic thermodynamics and modes of operation of a ribosome: a network theoretic perspective

The ribosome is one of the largest and most complex macromolecular machines in living cells. It polymerizes a protein in a step-by-step manner as directed by the corresponding nucleotide sequence on the template messenger RNA (mRNA) and this process is referred to as `translation' of the genetic message encoded in the sequence of mRNA transcript. In each successful chemo-mechanical cycle during the (protein) elongation stage, the ribosome elongates the protein by a single subunit, called amino acid, and steps forward on the template mRNA by three nucleotides called a codon. Therefore, a ribosome is also regarded as a molecular motor for which the mRNA serves as the track, its step size is that of a codon and two molecules of GTP and one molecule of ATP hydrolyzed in that cycle serve as its fuel. What adds further complexity is the existence of competing pathways leading to distinct cycles, branched pathways in each cycle and futile consumption of fuel that leads neither to elongation of the nascent protein nor forward stepping of the ribosome on its track. We investigate a model formulated in terms of the network of discrete chemo-mechanical states of a ribosome during the elongation stage of translation. The model is analyzed using a combination of stochastic thermodynamic and kinetic analysis based on a graph-theoretic approach. We derive the exact solution of the corresponding master equations. We represent the steady state in terms of the cycles of the underlying network and discuss the energy transduction processes. We identify the various possible modes of operation of a ribosome in terms of its average velocity and mean rate of GTP hydrolysis. We also compute entropy production as functions of the rates of the interstate transitions and the thermodynamic cost for accuracy of the translation process.

cond-mat.stat-mech

A Biologically Motivated Asymmetric Exclusion Process: interplay of congestion in RNA polymerase traffic and slippage of nascent transcript

We develope a theoretical framework, based on exclusion process, that is motivated by a biological phenomenon called transcript slippage (TS). In this model a discrete lattice represents a DNA strand while each of the particles that hop on it unidirectionally, from site to site, represents a RNA polymerase (RNAP). While walking like a molecular motor along a DNA track in a step-by-step manner, a RNAP simultaneously synthesizes a RNA chain; in each forward step it elongates the nascent RNA molecule by one unit, using the DNA track also as the template. At some special "slippery" position on the DNA, which we represent as a defect on the lattice, a RNAP can lose its grip on the nascent RNA and the latter's consequent slippage results in a final product that is either longer or shorter than the corresponding DNA template. We develope an exclusion model for RNAP traffic where the kinetics of the system at the defect site captures key features of TS events. We demonstrate the interplay of the crowding of RNAPs and TS. A RNAP has to wait at the defect site for longer period in a more congested RNAP traffic, thereby increasing the likelihood of its suffering a larger number of TS events. The qualitative trends of some of our results for a simple special case of our model are consistent with experimental observations. The general theoretical framework presented here will be useful for guiding future experimental queries and for analysis of the experimental data with more detailed versions of the same model.

cond-mat.stat-mech

A biologically motivated three-species exclusion model: effects of leaky scanning and overlapping genes on initiation of protein synthesis

Totally asymmetric simple exclusion process (TASEP) was originally introduced as a model for the traffic-like collective movement of ribosomes on a messenger RNA (mRNA) that serves as the track for the motor-like forward stepping of individual ribosomes. In each step, a ribosome elongates a protein by a single unit using the track also as a template for protein synthesis. But, pre-fabricated, functionally competent, ribosomes are not available to begin synthesis of protein; a subunit directionally scans the mRNA in search of the pre-designated site where it is supposed to bind with the other subunit and begin the synthesis of the corresponding protein. However, because of `leaky' scanning, a fraction of the scanning subunits miss the target site and continue their search beyond the first target. Sometimes such scanners successfully identify the site that marks the site for initiation of the synthesis of a different protein. In this paper, we develop an exclusion model, with three interconvertible species of hard rods, to capture some of the key features of these biological phenomena and study the effects of the interference of the flow of the different species of rods on the same lattice. More specifically, we identify the meantime for the initiation of protein synthesis as appropriate mean {\it first-passage} time that we calculate analytically using the formalism of backward master equations. In spite of the approximations made, our analytical predictions are in reasonably good agreement with the numerical data that we obtain by performing Monte Carlo simulations. We also compare our results with a few experimental facts reported in the literature and propose new experiments for testing some of our new quantitative predictions.

cond-mat.stat-mech

First-passage processes on a filamentous track in a dense traffic: optimizing diffusive search for a target in crowding conditions

Several important biological processes are initiated by the binding of a protein to a specific site on the DNA. The strategy adopted by a protein, called transcription factor (TF), for searching its specific binding site on the DNA has been investigated over several decades. In recent times the effects obstacles, like DNA-binding proteins, on the search by TF has begun to receive attention. RNA polymerase (RNAP) motors collectively move along a segment of the DNA during a genomic process called transcription. This RNAP traffic is bound to affect the diffusive scanning of the same segment of the DNA by a TF searching for its binding site. Motivated by this phenomenon, here we develop a kinetic model where a `particle', that represents a TF, searches for a specific site on a one-dimensional lattice. On the same lattice another species of particles, each representing a RNAP, hop from left to right exactly as in a totally asymmetric simple exclusion process (TASEP) which forbids simultaneous occupation of any site by more than one particle, irrespective of their identities. Although the TF is allowed to attach to or detach from any lattice site, the RNAPs can attach only to the first site at the left edge and detach from only the last site on the right edge of the lattice. We formulate the search as a {\it first-passage} process; the time taken to reach the target site {\it for the first time}, starting from a well defined initial state, is the search time. By approximate analytical calculations and Monte Carlo (MC) computer simulations, we calculate the mean search time. We show that RNAP traffic rectifies the diffusive motion of TF to that of a Brownian ratchet, and the mean time of successful search can be even shorter than that required in the absence of RNAP traffic. Moreover, we show that there is an optimal rate of detachment that corresponds to the shortest mean search time.

physics.bio-ph

Molecular force spectroscopy of kinetochore-microtubule attachment {\it in silico}: Mechanical signatures of an unusual catch bond and collective effects

Measurement of the life time of attachments formed by a single microtubule (MT) with a single kinetochore (kt) {\it in-vitro} under force-clamp conditions had earlier revealed a catch-bond-like behavior. In the past the physical origin of this apparently counter-intuitive phenomenon was traced to the nature of the force-dependence of the (de-)polymerization kinetics of the MTs. Here first the same model MT-kt attachment is subjected to external tension that increases linearly with time until rupture occurs. In our {\it force-ramp} experiments {\it in-silico}, the model displays the well known `mechanical signatures' of a catch-bond probed by molecular force spectroscopy. Exploiting this new evidence, we have further strengthened the analogy between MT-kt attachments and common ligand-receptor bonds in spite of the crucial differences in their underlying physical mechanisms. We then extend the formalism to model the stochastic kinetics of an attachment formed by a bundle of multiple parallel microtubules with a single kt considering the effect of rebinding under force-clamp and force-ramp conditions. From numerical studies of the model we predict the trends of variation of the mean life time and mean rupture force with the increasing number of MTs in the bundle. Both the mean life time and the mean rupture force display nontrivial nonlinear dependence on the maximum number of MTs that can attach simultaneously to the same kt.

physics.bio-ph

Fidelity of bacterial translation initiation: a stochastic kinetic model

During the initiation stage of protein synthesis, a ribosomal initiation complex (IC) is assembled on a messenger RNA (mRNA) template. In bacteria, the speed and accuracy of this assembly process are regulated by the complementary activities of three essential initiation factors (IFs). Selection of an authentic N-formylmethionyl-transfer RNA (fMet-tRNA\textsuperscript{fMet}) and the canonical, triplet-nucleotide mRNA start codon are crucial events during assembly of a canonical, ribosomal 70S IC. Mis-initiation due to the aberrant selection of an elongator tRNA or a non-canonical start codon are rare events that result in the assembly of a pseudo 70S IC or a non-canonical 70S IC, respectively. Here, we have developed a theoretical model for the stochastic kinetics of canonical-, pseudo-, and non-canonical 70S IC assembly that includes all of the major steps of the IC assembly process that have been observed and characterized in ensemble kinetic-, single-molecule kinetic-, and structural studies of the fidelity of translation initiation. Specifically, we use the rates of the individual steps in the IC assembly process and the formalism of first-passage times to derive exact analytical expressions for the probability distributions for the assembly of canonical-, pseudo- and non-canonical 70S ICs. In order to illustrate the power of this analytical approach, we compare the theoretically predicted first-passage time distributions with the corresponding computer simulation data. We also compare the mean times required for completion of these assemblies with experimental estimates. In addition to generating new, testable hypotheses, our theoretical model can also be easily extended as new experimental 70S IC assembly data become available, thereby providing a versatile tool for interpreting these data and developing advanced models of the mechanism and regulation of translation initiation.

physics.bio-ph

A biologically inspired two-species exclusion model: effects of RNA polymerase motor traffic on simultaneous DNA replication

We introduce a two-species exclusion model to describe the key features of the conflict between the RNA polymerase (RNAP) motor traffic, engaged in the transcription of a segment of DNA, concomitant with the progress of two DNA replication forks on the same DNA segment. One of the species of particles ($P$) represents RNAP motors while the other ($R$) represents replication forks. Motivated by the biological phenomena that this model is intended to capture, a maximum of only two $R$ particles are allowed to enter the lattice from two opposite ends whereas the unrestricted number of $P$ particles constitute a totally asymmetric simple exclusion process (TASEP) in a segment in the middle of the lattice. Consequently, the lattice consists of three segments; the encounters of the $P$ particles with the $R$ particles are confined within the middle segment (segment $2$) whereas only the $R$ particles can occupy the sites in the segments $1$ and $3$. The model captures three distinct pathways for resolving the co-directional as well as head-collision between the $P$ and $R$ particles. Using Monte Carlo simulations and heuristic analytical arguments that combine exact results for the TASEP with mean-field approximations, we predict the possible outcomes of the conflict between the traffic of RNAP motors ($P$ particles engaged in transcription) and the replication forks ($R$ particles). The outcomes, of course, depend on the dynamical phase of the TASEP of $P$ particles. In principle, the model can be adapted to the experimental conditions to account for the data quantitatively.

q-bio.SC