Biology subjects

Thiagarajan, R.

Publications and source records attributed to Thiagarajan, R..

5 recordsLinked to original sources

bioRxiv2026

Actin cross-linking organizes basal body patterning through anomalous diffusion transitions

Subcellular protein complexes and organelles exhibit diverse dynamic behaviors that reflect the mechanical constraints and organization of the intracellular environment. Although some structures follow classical Brownian motion, many display anomalous dynamics, including subdiffusion and superdiffusion, driven by viscoelasticity, molecular crowding, and cytoskeletal interactions. Transitions between these regimes are increasingly recognized as critical for subcellular organization, yet how they are regulated and influence pattern formation remains unclear. Here, we investigate the spatial arrangement of cilia on the apical surface of multiciliated cells (MCCs) in developing Xenopus laevis embryos, where coordinated ciliary beating depends on the precise organization of hundreds of centriole-derived basal bodies (BBs). Using quantitative confocal, high-resolution and high-speed TIRF imaging together with theoretical modeling, we show that BB trajectories undergo time-resolved transitions between diffusive and anomalous motion, with distinct regimes that correlate with apical surface expansion. During the early stages, actin remodeling facilitates the dispersal of BBs by providing a permissive, low-confinement environment. As development progresses, the actin network becomes increasingly cross-linked, forming a dense meshwork that constrains BB movement and promotes uniform spacing across the apical domain. Disruption of -actinin-1, a major actin cross-linking protein, impairs the integrity of the apical actin meshwork, weakens BB confinement, and disrupts regular spatial patterning, ultimately compromising the spatial arrangement of BBs required for proper cilia alignment. Together, we show that progressive apical actin cross-linking coordinates BB positioning and regulates their dynamic state, guiding the shift from diffusive to confined motion. This transition in dynamics enables the emergence of a uniform BB pattern, which in turn ensures the aligned deployment of motile cilia necessary for effective directional fluid flow.

biophysics↗

bioRxiv2022

Interplay between cell height variations and planar pulsations in epithelial monolayers

Biological tissues change their shapes through collective interactions of cells. This coordination sets length and time scales for dynamics where precision is essential, in particular during morphogenetic events. However, how these scales emerge remains unclear. Here we address this question using the pulsatile domains observed in confluent epithelial MDCK monolayers where cells exhibit synchronous contraction and extension cycles of {approx}5 hours duration and {approx}200 m length scale. We report that the monolayer thickness changes gradually in space and time by more than two folds in order to counterbalance the contraction and extension of the incompressible cytoplasm. We recapitulate these pulsatile dynamics using a continuum model and show that incorporation of cell stiffness dependent height variations is critical both for generating temporal pulsations and establishing the domain size. We propose that this feedback between height and mechanics could be important in coordinating the length scales of tissue dynamics.

biophysics↗

bioRxiv2021

Mechanics of cell integration in vivo

During embryonic development, regeneration and homeostasis, cells have to physically integrate into their target tissues, where they ultimately execute their function. Despite a significant body of research on how mechanical forces instruct cellular behaviors within the plane of an epithelium, very little is known about the mechanical interplay at the interface between migrating cells and their surrounding tissue, which has its own dynamics, architecture and identity. Here, using quantitative in vivo imaging and molecular perturbations, together with a theoretical model, we reveal that multiciliated cell (MCC) precursors in the Xenopus embryo form dynamic filopodia that pull at the vertices of the overlying epithelial sheet to probe their stiffness and identify the preferred positions for their integration into the tissue. Moreover, we report a novel function for a structural component of vertices, the lipolysis-stimulated lipoprotein receptor (LSR), in filopodia dynamics and show its critical role in cell intercalation. Remarkably, we find that pulling forces equip the MCCs to remodel the epithelial junctions of the neighboring tissue, enabling them to generate a permissive environment for their integration. Our findings reveal the intricate physical crosstalk at the cell-tissue interface and uncover previously unknown functions for mechanical forces in orchestrating cell integration.

biophysics↗

bioRxiv2020

Control and mechanisms of pulsatile flows in epithelial monolayers

Collective motions of epithelial cells in vivo are essential for morphogenesis in developmental biology. Tissues elongate, contract, flow, and oscillate, thus sculpting embryos. These tissue level dynamics are known, but the physical mechanisms at the cellular level are unclear, with various behaviors depending on the tissues and species. Moreover, investigations on in vitro tissue behavior usually focus on only one type of cell dynamics and use diverse theoretical approaches, making systematic comparisons between studies challenging. Here, we show that a single epithelial monolayer of Madin Darby Canine Kidney (MDCK) cells can exhibit two types of local tissue kinematics, pulsations and long range coherent flows. We analyzed these distinct motions by using quantitative live imaging. We also report that these motions can be controlled with internal and external cues such as specific inhibitors, and friction modulation of the substrate by microcontact printing method. We further demonstrate with a unified vertex model that both behaviors depend on the competition between velocity alignment and random diffusion of cell polarization. When alignment and diffusion are comparable, a pulsatile flow emerges, whereas the tissue undergoes long-range flows when velocity alignment dominates. We propose that environmental friction, acto-myosin distributions, and cell polarization kinetics are important in regulating the dynamics of tissue morphogenesis.

biophysics↗

bioRxiv2019

Cell motion as a stochastic process controlled by focal contacts dynamics.

Directed cell motion is essential in physiological and pathological processes such as morphogenesis, wound healing and cancer spreading. Chemotaxis has often been proposed as the driving mechanism, even though evidence of long-range gradients is often lacking in vivo. By patterning adhesive regions in space, we control cell shape and the associated potential to move along one direction in another mode of migration coined ratchetaxis. We report that focal contacts distributions collectively dictate cell directionality, and bias is non-linearly increased by gap distance between adhesive regions. Focal contact dynamics on micro-patterns allow to integrate these phenomena in a consistent model where each focal contact can be translated into a force with known amplitude and direction, leading to quantitative predictions for cell motion in every condition. Altogether, our study shows how local and minutes timescale dynamics of focal adhesions and their distribution lead to long term cellular motion with simple geometric rules.

biophysics↗