Biology subjects

Muhuri, S.

Publications and source records attributed to Muhuri, S..

4 recordsLinked to original sources

bioRxiv2026

Force Induces a Collective Inactivity in Dyneins to Auto-Regulate Bidirectional Transport of Vesicles

The back-and-forth (bidirectional) motion of Endosomes and Phagosomes along microtubules is fundamentally important for nutrient absorption, receptor recycling, pathogen degradation and many other downstream cellular pathways. Bidirectional motion requires opposing force from the kinesin and dynein motors, causing intermittent Tug-of-Wars (ToWs) followed by runs where winning motors drive their cargo until the next ToW. Dynein displays a counter-intuitive behaviour of catch bonding tightly to the microtubule against opposing force, but why such a response is needed remains unknown. Here we force dynein to catch-bond using an optical trap when dynein-teams are transporting phagosomes in-vitro and inside cells. An unexpected form of collective inactivity emerges, where larger dynein-teams remain inactive for longer after they have been catch-bonded. Kinesin exhibits a high probability of reversing the cargo during such periods of inactivity of dyneins. Therefore, the inactivity of dyneins allows cells to auto-regulate the effect of opposing molecular forces for the purpose of achieving bidirectional motion of endosomes/phagosomes. We propose that an inactivating conformational change is induced when dynein detaches against strain from its catch-bonded state. Collective inactivity follows because each inactive dynein exerts an entropic force on the other to delay the entire team from being activated. We capture the dynamics of this process through a statistical model of Entropically Constrained Reactivation, obtaining predictions in excellent agreement with experimental data. The emergent behaviour observed here possibly prevents a runaway dynein situation inside cells, its simple entropic origin suggesting broader relevance to catch-bonded receptor ligand interactions operating under conditions of cellular crowding.

cell biology↗

bioRxiv2022

Clustering and finite size effects in a two-species exclusion process

We study the cluster size distribution of particles for a two-species exclusion process which involves totally asymmetric transport process of two oppositely directed species with stochastic directional switching of the species on a 1D lattice. As a function of Q - the ratio of the translation rate and directional switching rate of particles, in the limit of Q [->] 0, the probability distribution of the cluster size is an exponentially decaying function of cluster size m and is exactly similar to the cluster size distribution of a TASEP. For Q >> 1, the model can be mapped to persistent exclusion process (PEP) and the average cluster size, [<]m[>] {propto} Q1/2. We obtain an approximate expression for the average cluster size in this limit. For finite system size system of L lattice sites, for a particle number density{rho} , the probability distribution of cluster sizes exhibits a distinct peak which corresponds to the formation of a single cluster of size ms ={rho} L. However this peak vanishes in the thermodynamic limit L [->] {infty}. Interestingly, the probability of this largest size cluster, P(ms), exhibits scaling behaviour such that in terms of scaled variable Q1 {equiv} Q/L2{rho}(1 -{rho} ), data collapse is observed for the probability of this cluster. The statistical features related to clustering observed for this minimal model may also be relevant for understanding clustering characteristics in active particles systems in confined 1D geometry.

biophysics↗

bioRxiv2022

Cargo transport by catchbonded 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.

biophysics↗

bioRxiv2018

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 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 provides a plausible resolution of the paradox of codependence.

biophysics↗