arXiv subjects

Ranjith Padinhateeri

Publications and source records attributed to Ranjith Padinhateeri.

7 recordsLinked to original sources

arXiv2021

Nucleosome sliding can influence the spreading of histone modifications

Nucleosomes are the fundamental building blocks of chromatin that not only help in the folding of chromatin but also in carrying epigenetic information. It is known that nucleosome sliding is responsible for dynamically organizing chromatin structure and the resulting gene regulation. Since sliding can move two neighboring nucleosomes physically close or away, can it play a role in the spreading of histone modifications? We investigate this by simulating a stochastic model that couples nucleosome dynamics with the kinetics of histone modifications. We show that the sliding of nucleosomes can affect the modification pattern as well as the time it takes to modify a given region of chromatin. Exploring different nucleosome densities and modification kinetic parameters, we show that nucleosome sliding can be important for creating histone modification domains. Our model predicts that nucleosome density coupled with sliding dynamics can create an asymmetric histone modification profile around regulatory regions. We also compute the probability distribution of modified nucleosomes and relaxation kinetics of modifications. Our predictions are comparable with known experimental results.

physics.bio-ph↗

arXiv2021

Heterogeneous interactions and polymer entropy decide organization and dynamics of chromatin domains

Chromatin is known to be organized into multiple domains of varying sizes and compaction. While these domains are often imagined as static structures, they are highly dynamic and show cell-to-cell variability. Since processes such as gene regulation and DNA replication occur in the context of these domains, it is important to understand their organization, fluctuation and dynamics. To simulate chromatin domains, one requires knowledge of interaction strengths among chromatin segments. Here, we derive interaction strength parameters from experimentally known contact maps and use them to predict chromatin organization and dynamics. Taking two domains on the human chromosome as examples, we investigate its 3D organization, size/shape fluctuations, and dynamics of different segments within a domain, accounting for hydrodynamic effects. Considering different cell types, we quantify changes in interaction strengths and chromatin shape fluctuations in different epigenetic states. Perturbing the interaction strengths systematically, we further investigate how epigenetic-like changes can alter the spatio-temporal nature of the domains. Our results show that heterogeneous weak interactions are crucial in determining the organization of the domains. Computing effective stiffness and relaxation times, we investigate how perturbations in interactions affect the solid-like and liquid-like nature of chromatin domains. Quantifying dynamics of chromatin segments within a domain, we show how the competition between polymer entropy and interaction energy influence the timescales of loop formation and maintenance of stable loops.

cond-mat.soft↗

arXiv2020

High fidelity epigenetic inheritance: Information theoretic model predicts $k$-threshold filling of histone modifications post replication

Beyond the genetic code, there is another layer of information encoded as chemical modifications on histone proteins positioned along the DNA. Maintaining these modifications is crucial for survival and identity of cells. How the information encoded in the histone marks gets inherited, given that only half the parental nucleosomes are transferred to each daughter chromatin, is a puzzle. We address this problem using ideas from Information theory and understanding from recent biological experiments. Mapping the replication and reconstruction of modifications to equivalent problems in communication, we ask how well an enzyme-machinery can recover information, if they were ideal computing machines. Studying a parameter regime where realistic enzymes can function, our analysis predicts that, pragmatically, enzymes may implement a threshold$-k$ filling algorithm which derives from maximum à posteriori probability decoding. Simulations using our method produce modification patterns similar to what is observed in recent experiments.

q-bio.GN↗

arXiv2016

Sufficient conditions for the additivity of stall forces generated by multiple filaments or motors

Molecular motors and cytoskeletal filaments work collectively most of the time under opposing forces. This opposing force may be due to cargo carried by motors or resistance coming from the cell membrane pressing against the cytoskeletal filaments. Some recent studies have shown that the collective maximum force (stall force) generated by multiple cytoskeletal filaments or molecular motors may not always be just a simple sum of the stall forces of the individual filaments or motors. To understand this excess or deficit in the collective force, we study a broad class of models of both cytoskeletal filaments and molecular motors. We argue that the stall force generated by a group of filaments or motors is additive, that is, the stall force of $N$ number of filaments (motors) is $N$ times the stall force of one filament (motor), when the system is in equilibrium at stall. Conversely, we show that this additive property typically does not hold true when the system is not at equilibrium at stall. We thus present a novel and unified understanding of the existing models exhibiting such non-addivity, and generalise our arguments by developing new models that demonstrate this phenomena. We also propose a quantity similar to thermodynamic efficiency to easily predict this deviation from stall-force additivity for filament and motor collectives.

cond-mat.soft↗

arXiv2014

Collective force generated by multiple biofilaments can exceed the sum of forces due to individual ones

Collective dynamics and force generation by cytoskeletal filaments are crucial in many cellular processes. Investigating growth dynamics of a bundle of N independent cytoskeletal filaments pushing against a wall, we show that chemical switching (ATP/GTP hydrolysis) leads to a collective phenomenon that is currently unknown. Obtaining force-velocity relations for different models that capture chemical switching, we show, analytically and numerically, that the collective stall force of N filaments is greater than N times the stall force of a single filament. Employing an exactly solvable toy model, we analytically prove the above result for N=2. We, further, numerically show the existence of this collective phenomenon, for N>=2, in realistic models (with random and sequential hydrolysis) that simulate actin and microtubule bundle growth. We make quantitative predictions for the excess forces, and argue that this collective effect is related to the non-equilibrium nature of chemical switching.

physics.bio-ph↗

arXiv2014

Force-induced dynamical properties of multiple cytoskeletal filaments are distinct from that of single filaments

How cytoskeletal filaments collectively undergo growth and shrinkage is an intriguing question. Collective properties of multiple bio-filaments (actin or microtubules) undergoing hydrolysis, have not been studied extensively earlier, within simple theoretical frameworks. In this paper, we show that collective properties of multiple filaments under force are very distinct from the properties of a single filament under similar conditions -- these distinctions manifest as follows: (i) the collapse time during collective catastrophe for a multifilament system is much larger than that of a single filament with the same average length, (ii) force-dependence of the cap-size distribution of multiple filaments are quantitatively different from that of single filament, (iii) the diffusion constant associated with the system length fluctuations is distinct for multiple filaments, (iv) switching dynamics of multiple filaments between capped and uncapped states and the fluctuations therein are also distinct. We build a unified picture by establishing interconnections among all these collective phenomena. Additionally, we show that the collapse times during catastrophes can be sharp indicators of collective stall forces exceeding the additive contributions of single filaments.

physics.bio-ph↗

arXiv2011

The random release of phosphate controls the dynamic instability of microtubules

A simple stochastic model which describes microtubule dynamics and explicitly takes into account the relevant biochemical processes is presented. The model incorporates binding and unbinding of monomers and random phosphate release inside the polymer. It is shown that this theoretical approach provides a microscopic picture of the dynamic instability phenomena of microtubules. The cap size, the concentration dependence of the catastrophe times and the delay before observing catastrophes following a dilution can be quantitatively predicted by this approach in a direct and simple way. Furthermore, the model can be solved analytically to a large extend, thus offering a valuable starting point for more refined studies of microtubules dynamics.

cond-mat.stat-mech↗