Biology subjects

Mohapatra, L.

Publications and source records attributed to Mohapatra, L..

5 recordsLinked to original sources

bioRxiv2025

Hydrolysis-dependent severing tunes internal monomeric heterogeneity to shape actin length distributions

The coordination of actin-binding proteins (ABPs) is essential for forming a wide range of actin structures that drive vital cellular processes. Many of the ABPs, like the severing protein cofilins, exhibit affinities dependent on the nucleotide state of actin monomers. Experiments have shown that cofilins interact with actin filaments cooperatively in a concentration-dependent manner, where it severs less at both low and high concentrations. However, how this nucleotide state-dependent severing influences actin filament distributions is poorly understood. Here, we propose a computational model of actin filament dynamics that combines stochastic polymerization, phosphate release, hydrolysis-dependent cooperative binding of cofilins, and severing of actin monomers. This model simultaneously reproduces key experimentally observed features: The non-monotonic change of the filament length and the monotonic decay in actin cap size with the increasing cofilin concentration, as well as the linear increase of the cap size with the actin concentration. We elucidate how both these emerge from the tuning of the heterogeneity in the arrangement of cofilin decorated and undecorated monomers within a filament. We also predict that, with varying cofilin concentrations, steady-state length distributions can change from symmetric bell-shaped to long-tailed skewe d shapes. We show that, in some regimes, our model simplifies to a coarse-grained model enabling us to mathematically predict that the distribution of undecorated monomers is exponential with a decay exponent that depends on cofilin and actin concentration. This study highlights the importance of non equilibrium processes that can modulate structural heterogeneity within a filament to shape actin length variation.

biophysics↗

bioRxiv2025

Quantitative Signatures of Disassembly Mechanisms Modulating Filament and Bundle Assembly in a Shared Pool

How cytoskeletal structures control their assembly while sharing a common pool of their constituent parts is an open question in biology. Experiments indicate that mechanisms promoting the disassembly of these structures and replenishing the pool may play a vital role. Here, we compare the role of two modes of disassembly: monomer loss and loss of fragments (severing), in the assembly of bare filaments and bundles, modeled as a collection of linear filaments. Using analytical calculations and simulations, we show that severing can accelerate the assembly of these structures and ensure their precise size control in a shared pool. We also examine their length fluctuations and find that the decay in the autocorrelation function is faster with severing. Our study identifies parameters that influence assembly kinetics as well as the decay in autocorrelations of length fluctuations. These findings provide a framework for designing experiments that can differentiate between size control mechanisms in cytoskeletal structures.

biophysics↗

bioRxiv2024

Transcription templated assembly of the nucleolus in the C. elegans embryo

The nucleolus is a multicomponent structure made of RNA and proteins that serves as the site of ribosome biogenesis within the nucleus. It has been extensively studied as a prototype of a biomolecular condensate whose assembly is driven by phase separation. While the steady-state size of the nucleolus is quantitatively accounted for by the thermodynamics of phase separation, we show that experimental measurements of the assembly dynamics are inconsistent with a simple model of a phase-separating system relaxing to its equilibrium state. Instead, we show that the dynamics are well described by a model in which the transcription of ribosomal RNA actively drives nucleolar assembly. We find that our model of active transcription-templated assembly quantitatively accounts for the rapid kinetics observed in early embryos at different developmental stages, and for different RNAi perturbations of embryo size. Our model predicts a scaling of the time to assembly with the volume of the nucleus to the one-third power, which is confirmed by experimental data. Our study highlights the role of active processes such as transcription in controlling the placement and timing of assembly of membraneless organelles. Significance statementHow membraneless organelles like nucleolus assemble within cells is not well understood. Recent experiments suggest that transcription of ribosomal RNA actively drives nucleolar assembly. Our proposed model of active transcription-templated assembly quantitatively accounts for the rapid kinetics observed in early worm embryos at different developmental stages. Further, it predicts a scaling of the time to assembly with the volume of the nucleus that is confirmed by experimental data. This work describes how active processes such as transcription can control the placement and timing of assembly of membraneless organelles.

cell biology↗

bioRxiv2022

Competition between severing and tubulin induced repair of microtubules

Cytoskeletal structures aid in cell polarization, motility, and intracellular transport. Their functions are predicated on the rapid turnover of cytoskeleton proteins, which is achieved by the coordinated effort of multiple regulatory proteins whose dynamics are not well understood. In-vitro experiments have shown that free tubulin can repair nanoscale damages of microtubules created by severing proteins. Based on this observation, we propose a model for microtubule severing as a competition between the processes of damage spreading and tubulin-induced repair. Using theory and simulations, we demonstrate that this model is in quantitative agreement with in vitro experiments. We predict the existence of a critical tubulin concentration above which severing becomes rare but fast, and hypersensitive to the concentration of free tubulin. Further we show that this hypersensitivity leads to a dramatic increase in the dynamic range of steady-state microtubule lengths, when lengths are controlled by severing. Our work demonstrates how synergy between tubulin and severing proteins can lead to novel dynamical properties of microtubules.

cell biology↗

bioRxiv2018

Length regulation of multiple flagella that self-assemble from a shared pool of components

Control of organelle size is a problem that has intrigued cell biologists for at least a century. The single-celled green algae Chlamydomonas reinhardtii with its two 2agella has proved to be a very useful model organism for studies of size control. Numerous experiments have identi1ed motor-driven transport of tubulin to the growing ends of microtubules at the tip of the 2agella as the key component of the machinery responsible for controlling their length. Here we consider a model of 2agellar length control whose key assumption is that proteins responsible for the intra2agellar transport (IFT) of tubulin are present in limiting amounts. We show that this limiting-pool assumption and simple reasoning based on the law of mass action leads to an inverse relationship between the rate at which a 2agellum grows and its length, which has been observed experimentally, and has been shown theoretically to provide a mechanism for length control. Experiments in which one of the two 2agella are severed have revealed the coupled nature of the growth dynamics of the two 2agella, and we extend our length-control model to two 2agella by considering different mechanisms of their coupling. We describe which coupling mechanisms are capable of reproducing the observed dynamics in severing experiments, and why some that have been proposed previously are not. Within our theoretical framework we conclude that if tubulin and IFT proteins are freely exchanged between 2agella simultaneous length control is not possible if the disassembly rate is constant. However, if disassembly depends on the concentration of IFT proteins at the tip of the 2agellum, simultaneous length control can be achieved. Finally, we make quantitative predictions for experiments that could test this model.

systems biology↗