Biology subjects

Chelakkot, R.

Publications and source records attributed to Chelakkot, R..

6 recordsLinked to original sources

bioRxiv2022

Role of Delta-Notch signalling molecules on cell-cell adhesion in determining heterogeneous chemical and cell morphological patterning

Cell mechanics and motility are responsible for collective motion of cells that result in overall deformation of epithelial tissues. On the other hand, contact-dependent cell-cell signalling is responsible for generating a large variety of intricate, self-organized, spatial patterns of the signalling molecules. Moreover, it is becoming increasingly clear that the combined mechanochemical patterns of cell shape/size and signalling molecules in the tissues, for example, in cancerous and sensory epithelium, are governed by mechanochemical coupling between chemical signalling and cell mechanics. However, a clear quantitative picture of how these two aspects of tissue dynamics, i.e., signalling and mechanics, lead to pattern and form is still emerging. Although, a number of recent experiments demonstrate that cell mechanics, cell motility, and cell-cell signalling are tightly coupled in many morphogenetic processes, relatively few modeling efforts have focused on an integrated approach. We extend the vertex model of an epithelial monolayer to account for contact-dependent signalling between adjacent cells and between non-adjacent neighbors through long protrusional contacts with a feedback mechanism wherein the adhesive strength between adjacent cells is controlled by the expression of the signalling molecules in those cells. Local changes in cell-cell adhesion lead to changes in cell shape and size, which in turn drives changes in the levels of signalling molecules. Our simulations show that even this elementary two-way coupling of chemical signalling and cell mechanics is capable of giving rise to a rich variety of mechanochemical patterns in epithelial tissues. In particular, under certain parametric conditions, bimodal distributions in cell size and shape are obtained, which resemble experimental observations in cancerous and sensory tissues.

biophysics↗

bioRxiv2021

Effective elasticity and persistence of strain in active filament-motor assemblies

Cross-linked composite filaments animated by molecular motors are ubiquitous in biology. An important length scale that controls the range of force transmission in these filament-motor assemblies is the distance over which elastic strain fields persist. Previous studies have identified this persistence or decay length in passive networks, and recently, in random elastic networks with embedded elements generating constant forces or stresses. Yet, the range over which strains persist in assembles comprised of motors attaching stochastically to nearly inextensible filaments remains unclear. Here, we analyze the intrinsic decay length for extensional strain in a minimal model - ordered composite assemblies comprised of cross-linked filaments interacting with arrayed motors. We explores three related concepts: the effective active elasticity of these assembles, the length scale over which localized elastic strains persist in these systems, and its dependence on motor kinetics for static and oscillatory deformations. By combining mean-field theory for noiseless weakly extensible systems with Multi-Particle Collision Brownian simulations for noisy systems we are able to additionally investigate the effects of motor noise. For steady strains, we find that the persistence length is independent of motor kinetics and dependent on the passive elasticity of the composite. For oscillatory strains, the persistence length is frequency dependent and depends on passive elasticity and on motor kinetics. For strong motor activity, the decay length is significantly modulated by extensional softening resulting from attached motors. Theoretical predictions agree qualitatively with our simulations, even at low motor numbers or moderately strong motor noise. Taken together, our results highlight how extensional strain and correlated dynamics in possess a finite range of influence even in active networks comprised of nearly inextensible filaments.

biophysics↗

bioRxiv2020

Role of cell polarity dynamics and motility in pattern formation due to contact dependent signalling

A key challenge in biology is to understand how spatiotemporal patterns and structures arise during the development of an organism. An initial aggregate of spatially uniform cells develops and forms the differentiated structures of a fully developed organism. On the one hand, contact-dependent cell-cell signalling is responsible for generating a large number of complex, self-organized, spatial patterns in the distribution of the signalling molecules. On the other hand, the motility of cells coupled with their polarity can independently lead to collective motion patterns that depend on mechanical parameters influencing tissue deformation, such as cellular elasticity, cell-cell adhesion and active forces generated by actin and myosin dynamics. Although modelling efforts have, thus far, treated cell motility and cell-cell signalling separately, experiments in recent years suggest that these processes could be tightly coupled. Hence, in this paper, we study how the dynamics of cell polarity and migration influence the spatiotemporal patterning of signalling molecules. Such signalling interactions can occur only between cells that are in physical contact, either directly at the junctions of adjacent cells or through cellular protrusional contacts. We present a vertex model which accounts for contact-dependent signalling between adjacent cells and between non-adjacent neighbours through long protrusional contacts that occur along the orientation of cell polarization. We observe a rich variety of spatiotemporal patterns of signalling molecules that is influenced by polarity dynamics of the cells, relative strengths of adjacent and non-adjacent signalling interactions, range of polarized interaction, signalling activation threshold, relative time scales of signalling and polarity orientation, and cell motility. Though our results are developed in the context of Delta-Notch signalling, they are sufficiently general and can be extended to other contact dependent morpho-mechanical dynamics.

biophysics↗

bioRxiv2020

Synchronized oscillations, metachronal waves, and jammed clusters in sterically interacting active filament arrays

Autonomous active, elastic filaments that interact with each other to achieve cooperation and synchrony underlie many critical functions in biology. A striking example is ciliary arrays in the mammalian respiratory tract; here individual filaments communicate through direct interactions and through the surrounding fluid to generate metachronal traveling waves crucial for mucociliary clearance. The mechanisms underlying this collective response and the essential ingredients for stable synchronization remain a mystery. In this article, we describe Brownian dynamics simulations of multi-filament arrays, demonstrating that short-range steric inter-filament interactions and surface-roughness are sufficient to generate a rich variety of collective spatiotemporal oscillatory, traveling and static patterns. Starting from results for the collective dynamics of two- and three-filament systems, we identify parameter ranges in which inter-filament interactions lead to synchronized oscillations. We then study how these results generalize to large one-dimensional arrays of many interacting filaments. The phase space characterizing the multi-filament array dynamics and deformations exhibits rich behaviors, including oscillations and traveling metachronal waves, depending on the interplay between geometric spacing between filaments, activity, and elasticity of the filaments. Interestingly, the existence of metachronal waves is nonmonotonic with respect to the inter-filament spacing. We also find that the degree of filament surface roughness significantly affects the dynamics -- roughness on scales comparable to the filament thickness generates a locking-mechanism that transforms traveling wave patterns into statically stuck and jammed configurations. Our simulations suggest that short-ranged steric inter-filament interactions are sufficient and perhaps even critical for the development, stability and regulation of collective patterns.

biophysics↗

bioRxiv2019

Instabilities and Spatiotemporal Dynamics of Active Elastic Filaments

Biological filaments driven by molecular motors tend to experience tangential propulsive forces also known as active follower forces. When such a filament encounters an obstacle, it deforms, which reorients its follower forces and alters its entire motion. If the filament pushes a cargo, the friction on the cargo can be enough to deform the filament, thus affecting the transport properties of the cargo. Motivated by cytoskeletal filament motility assays, we study the dynamic buckling instabilities of a two-dimensional slender elastic filament driven through a dissipative medium by tangential propulsive forces in the presence of obstacles or cargo. We observe two distinct instabilities. When the filaments head is pinned or experiences significant translational but little rotational drag from its cargo, it buckles into a steadily rotating coiled state. When it is clamped or experiences both significant translational and rotational drag from its cargo, it buckles into a periodically beating, overall translating state. Using minimal analytically tractable models, linear stability theory, and fully non-linear computations, we study the onset of each buckling instability, characterize each buckled state, and map out the phase diagram of the system. Finally, we use particle-based Brownian dynamics simulations to show our main results are robust to moderate noise and steric repulsion. Overall, our results provide a unified framework to understand the dynamics of tangentially propelled filaments and filament-cargo assemblies.

biophysics↗

bioRxiv2018

Filament extensibility and shear stiffening control persistence of strain and loss of coherence in cross-linked motor-filament assemblies

Cross-linked flexible filaments deformed by active molecular motors occur in many natural and synthetic settings including eukaryotic flagella, the cytoskeleton and in vitro motor assays. In these systems, an important quantity that controls spatial coordination and emergent collective behavior is the length scale over which elastic strains persist. We estimate this quantity in the context of ordered composites comprised of cross-linked elastic filaments sheared by active motors. Combining a mean-field theory valid for negligibly noisy systems with discrete simulations for noisy systems, we show that the effect of localized strains - be they steady or oscillatory - persist over distances determined by motor kinetics, motor elasticity and filament extensibility. The cut-off length that emerges from these effects controls the transmission of mechanical information and determines the criterion for spatially separated motor groups to stay synchronized. Our results generalize the notion of persistence in passive, Brownian filaments to active, cross-linked filaments.

biophysics↗