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Mandar M. Inamdar

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Published work

5 published item(s)

preprint2026arXiv

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. The transitions between these regimes are increasingly recognized as critical for subcellular organization, yet how they 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 that constrains BB movement and promotes uniform spacing across the apical domain. Disruption of $α$-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 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.

preprint2016arXiv

Coherent motion of monolayer sheets under confinement and its pathological implications

Coherent angular rotation of epithelial cells is thought to contribute to many vital physiological processes including tissue morphogenesis and glandular formation. However, factors regulating this motion, and the implications of this motion if perturbed remain incompletely understood. In the current study, we address these questions using a cell-center based model in which cells are polarized, motile, and interact with the neighboring cells via harmonic forces. We demonstrate that, a simple evolution rule in which the polarization of any cell tends to orient with its velocity vector can induce coherent motion in geometrically confined environments. In addition to recapitulating coherent rotational motion observed in experiments, our results also show the presence of radial movements and tissue behavior that can vary between solid-like and fluid-like. We show that the pattern of coherent motion is dictated by the combination of different physical parameters including number density, cell motility, system size, bulk cell stiffness and stiffness of cell-cell adhesions. We further observe that, perturbations in the form of cell division can induce a reversal in the direction of motion when cell division occurs synchronously. Moreover, when the confinement is removed, we see that the existing coherent motion leads to cell scattering, with bulk cell stiffness and stiffness of cell-cell contacts dictating the invasion pattern. In summary, our study provides an in-depth understanding of the origin of coherent rotation in confined tissues, and extracts useful insights into the influence of various physical parameters on the pattern of such movements

preprint2013arXiv

Spatial anisotropy and heterogeneity in contractility and adhesion distribution may contribute to cell steering during migration

Transition from random to persistent cell motility requires spatiotemporal organization of the cytoskeleton and focal adhesions. The influence of these two structures on cell steering can also be gleaned from trypsin de-adhesion experiments, wherein cells exposed to trypsin round up, exhibiting a combination of rotation and translation. Here, we present a model to evaluate the contributions of contractility and bond distribution to experimentally observed de-adhesion. We show that while asymmetry in bond distribution causes only cell translation, a combination of asymmetric bond distribution and non-uniform contractility are required for translation and rotation, and may guide cell migration.

preprint2012arXiv

Broad-tailed force distributions and velocity ordering in a heterogeneous membrane model for collective cell migration

Correlated velocity patterns and associated large length-scale transmission of traction forces have been observed in collective live cell migration as a response to a "wound". We argue that a simple physical model of a force-driven heterogeneous elastic membrane sliding over a viscous substrate can qualitatively explain a few experimentally observed facts: (i) the growth of velocity ordering which spreads from the wound boundary to the interior, (ii) the exponential tails of the traction force distributions, and (iii) the swirling pattern of velocities in the interior of the tissue.

preprint2005arXiv

Teaching the Principles of Statistical Dynamics

We describe a simple framework for teaching the principles that underlie the dynamical laws of transport: Fick's law of diffusion, Fourier's law of heat flow, the Newtonian viscosity law, and mass-action laws of chemical kinetics. In analogy with the way that the maximization of entropy over microstates leads to the Boltzmann law and predictions about equilibria, maximizing a quantity that E. T. Jaynes called "Caliber" over all the possible microtrajectories leads to these dynamical laws. The principle of Maximum Caliber also leads to dynamical distribution functions which characterize the relative probabilities of different microtrajectories. A great source of recent interest in statistical dynamics has resulted from a new generation of single-particle and single-molecule experiments which make it possible to observe dynamics one trajectory at a time.