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Mithun K. Mitra

Publications and source records attributed to Mithun K. Mitra.

9 recordsLinked to original sources

Nature of barriers determine first passage times in heterogeneous media

Intuition suggests that passage times across a region increases with the number of barriers along the path. Can this fail depending on the nature of the barrier? To probe this fundamental question, we exactly solve for the first passage time in general d-dimensions for diffusive transport through a spatially patterned array of obstacles - either entropic or energetic, depending on the nature of the obstacles. For energetic barriers, we show that first passage times vary non-monotonically with the number of barriers, while for entropic barriers it increases monotonically. This non-monotonicity for energetic barriers further reflects in the behaviour of effective diffusivity as well. We then design a simple experiment where a robotic bug navigates a heterogeneous environment through a spatially patterned array of obstacles to validate our predictions. Finally, using numerical simulations, we show that this non-monotonic behaviour for energetic barriers is general and extends to even super-diffusive transport.

cond-mat.stat-mech

Theoretical analysis of cargo transport by catch bonded motors in optical trapping assays

Dynein motors exhibit catch bonding, where the unbinding rate of the motors from microtubule filaments decreases with increasing opposing load. The implications of this catch bond on the transport properties of dynein-driven cargo are yet to be fully understood. In this context, optical trapping assays constitute an important means of accurately measuring the forces generated by molecular motor proteins. We investigate, using theory and stochastic simulations, the transport properties of cargo transported by catch bonded dynein molecular motors - both singly and in teams - in a harmonic potential, which mimics the variable force experienced by cargo in an optical trap. We estimate the biologically relevant measures of first passage time - the time during which the cargo remains bound to the microtubule and detachment force -the force at which the cargo unbinds from the microtubule, using both two-dimensional and one-dimensional force balance frameworks. Our results suggest that even for cargo transported by a single motor, catch bonding may play a role depending on the force scale which marks the onset of the catch bond. By comparing with experimental measurements on single dynein-driven transport, we estimate realistic bounds of this catch bond force scale. Generically, catch bonding results in increased persistent motion, and can also generate non-monotonic behaviour of first passage times. For cargo transported by multiple motors, emergent collective effects due to catch bonding can result in non-trivial re-entrant phenomena wherein average first passage times and detachment forces exhibit non-monotonic behaviour as a function of the stall force and the motor velocity.

physics.bio-ph

An India-specific Compartmental Model for Covid-19: Projections and Intervention Strategies by Incorporating Geographical, Infrastructural and Response Heterogeneity

We present a compartmental meta-population model for the spread of Covid-19 in India. Our model simulates populations at a district or state level using an epidemiological model that is appropriate to Covid-19. Different districts are connected by a transportation matrix developed using available census data. We introduce uncertainties in the testing rates into the model that takes into account the disparate responses of the different states to the epidemic and also factors in the state of the public healthcare system. Our model allows us to generate qualitative projections of Covid-19 spread in India, and further allows us to investigate the effects of different proposed interventions. By building in heterogeneity at geographical and infrastructural levels and in local responses, our model aims to capture some of the complexity of epidemiological modeling appropriate to a diverse country such as India.

q-bio.PE

Dynein catch bond as a mediator of codependent bidirectional cellular transport

Intracellular bidirectional transport of cargo on microtubule filaments is achieved by the collective action of oppositely directed dynein and kinesin motors. Experiments have found that in certain cases, inhibiting the activity of one type of motor results in an overall decline in the motility of the cellular cargo in both directions. This counter-intuitive observation, referred to as {\em paradox of codependence} is inconsistent with the existing paradigm of a mechanistic tug-of-war between oppositely directed motors. Unlike kinesin, dynein motors exhibit catchbonding, wherein the unbinding rates of these motors decrease with increasing force on them. Incorporating this catchbonding behavior of dynein in a theoretical model, we show that the functional divergence of the two motors species manifests itself as an internal regulatory mechanism, and leads to codependent transport behaviour in biologically relevant regimes. Using analytical methods and stochastic simulations, we analyse the processivity characteristics and probability distribution of run times and pause times of transported cellular cargoes. We show that catchbonding can drastically alter the transport characteristics and also provide a plausible resolution of the paradox of codependence.

physics.bio-ph

Diffusion dynamics and steady states of systems of hard rods on the square lattice

It is known from grand canonical simulations of a system of hard rods on two dimensional lattices that an orientationally ordered nematic phase exists only when the length of the rods is at least seven. However, a recent microcanonical simulation with diffusion kinetics, conserving both total density and zero nematic order, reported the existence of a nematically phase segregated steady state with interfaces in the diagonal direction for rods of length six [Phys. Rev. E 95, 052130 (2017)], violating the equivalence of different ensembles for systems in equilibrium. We resolve this inconsistency by demonstrating that the kinetics violate detailed balance condition and drives the system to a nonequilibrium steady state. By implementing diffusion kinetics that drives the system to equilibrium, even within this constrained ensemble, we recover earlier results showing phase segregation only for rods of length greater than or equal to seven. Furthermore, in contrast to the nonequilibrium steady state, the interface has no preferred orientational direction. In addition, by implementing different nonequilibrium kinetics, we show that the interface between the phase segregated states can lie in different directions depending on the choice of kinetics.

cond-mat.soft

Delayed self-regulation leads to novel states in epigenetic landscapes

The epigenetic pathway of a cell as it differentiates from a stem cell state to a mature lineage-committed one has been historically understood in terms of Waddington's landscape, consisting of hills and valleys. The smooth top and valley-strewn bottom of the hill represents their undifferentiated and differentiated states respectively. Although mathematical ideas rooted in nonlinear dynamics and bifurcation theory have been used to quantify this picture, the importance of time delays arising from multistep chemical reactions or cellular shape transformations have been ignored so far. We argue that this feature is crucial in understanding cell differentiation and explore the role of time delay in a model of a single gene regulatory circuit. We show that the interplay of time-dependant drive and delay introduces a new regime where the system shows sustained oscillations between the two admissible steady states. We interpret these results in the light of recent perplexing experiments on inducing the pluripotent state in mouse somatic cells. We also comment on how such an oscillatory state can provide a framework for understanding more general feedback circuits in cell development.

q-bio.CB

Thermodynamic behaviour of two-dimensional vesicles revisited

We study pressurised self-avoiding ring polymers in two dimensions using Monte Carlo simulations, scaling arguments and Flory-type theories, through models which generalise the model of Leibler, Singh and Fisher [Phys. Rev. Lett. Vol. 59, 1989 (1987)]. We demonstrate the existence of a thermodynamic phase transition at a non-zero scaled pressure $\tilde{p}$, where $\tilde{p} = Np/4π$, with the number of monomers $N \rightarrow \infty$ and the pressure $p \rightarrow 0$, keeping $\tilde{p}$ constant, in a class of such models. This transition is driven by bond energetics and can be either continuous or discontinuous. It can be interpreted as a shape transition in which the ring polymer takes the shape, above the critical pressure, of a regular N-gon whose sides scale smoothly with pressure, while staying unfaceted below this critical pressure. In the general case, we argue that the transition is replaced by a sharp crossover. The area, however, scales with $N^2$ for all positive $p$ in all such models, consistent with earlier scaling theories.

cond-mat.stat-mech

Asymptotic Behavior of Inflated Lattice Polygons

We study the inflated phase of two dimensional lattice polygons with fixed perimeter $N$ and variable area, associating a weight $\exp[pA - Jb ]$ to a polygon with area $A$ and $b$ bends. For convex and column-convex polygons, we show that $ /A_{max} = 1 - K(J)/\tilde{p}^2 + \mathcal{O}(ρ^{-\tilde{p}})$, where $\tilde{p}=pN \gg 1$, and $ρ<1$. The constant $K(J)$ is found to be the same for both types of polygons. We argue that self-avoiding polygons should exhibit the same asymptotic behavior. For self-avoiding polygons, our predictions are in good agreement with exact enumeration data for J=0 and Monte Carlo simulations for $J \neq 0$. We also study polygons where self-intersections are allowed, verifying numerically that the asymptotic behavior described above continues to hold.

cond-mat.stat-mech

Phase Transitions in Pressurised Semiflexible Polymer Rings

We propose and study a model for the equilibrium statistical mechanics of a pressurised semiflexible polymer ring. The Hamiltonian has a term which couples to the algebraic area of the ring and a term which accounts for bending (semiflexibility). The model allows for self-intersections. Using a combination of Monte Carlo simulations, Flory-type scaling theory, mean-field approximations and lattice enumeration techniques, we obtain a phase diagram in which collapsed and inflated phases are separated by a continuous transition. The scaling properties of the averaged area as a function of the number of units of the ring are derived. For large pressures, the asymptotic behaviour of the area is calculated for both discrete and lattice versions of the model. For small pressures, the area is obtained through a mapping onto the quantum mechanical problem of an electron moving in a magnetic field. The simulation data agree well with the analytic and mean-field results.

cond-mat.stat-mech