Searcharxiv⌕ Search

arXiv subjects

Mandar M. Inamdar

Publications and source records attributed to Mandar M. Inamdar.

14 recordsLinked to original sources
arXiv2026

Forces at the scale of the cell

The importance of molecular-scale forces in sculpting biological form and function has been acknowledged for more than a century. Accounting for forces in biology is a problem that lies at the intersection of soft condensed matter physics, statistical mechanics, and experimental methods, all adapted to a cellular context. This review surveys how forces arise within the cell. We provide a summary of the relevant background in cell biophysics, of soft-matter systems in and out of thermodynamic equilibrium, and of various force measurement methods. These ideas are then deployed to describe how forces are generated, transmitted, and sensed in specific cell-scale processes. We emphasize active matter descriptions, methodological tools that provide ways of incorporating non-equilibrium effects in a systematic manner into conceptual as well as quantitative descriptions. Our examples include polymerization forces, the motion of molecular motors, the properties of the actomyosin cortex, the mechanics of cell division, and shape changes in tissues. We suggest that a deeper understanding of cell function will necessarily require integrating the action of cell-scale physical forces with the assimilation and processing of information.

cond-mat.soft↗
arXiv2026

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.

cond-mat.soft↗
arXiv2022

Active T1 transitions in cellular networks

In amorphous solids as in tissues, neighbor exchanges can relax local stresses and allow the material to flow. In this paper, we use an anisotropic vertex model to study T1 rearrangements in polygonal cellular networks. We consider two different physical realizations of the active anisotropic stresses: (i) anisotropic bond tension and (ii) anisotropic cell stress. Interestingly, the two types of active stress lead to patterns of relative orientation of T1 transitions and cell elongation that are different. Our work suggests that these two realizations of anisotropic active stresses can be observed \textit{in vivo}. We describe and explain these results through the lens of a continuum description of the tissue as an anisotropic active material. We furthermore discuss the energetics of the dynamic tissue and express the energy balance in terms of internal elastic energy, mechanical work, chemical work and heat. This allows us to define active T1 transitions that can perform mechanical work while consuming chemical energy.

physics.bio-ph↗
arXiv2021

Nonlinear rheology of cellular networks

Morphogenesis depends crucially on the complex rheological properties of cell tissues and on their ability to maintain mechanical integrity while rearranging at long times. In this paper, we study the rheology of polygonal cellular networks described by a vertex model in the presence of fluctuations. We use a triangulation method to decompose shear into cell shape changes and cell rearrangements. Considering the steady-state stress under constant shear, we observe nonlinear shear-thinning behavior at all magnitudes of the fluctuations, and an even stronger nonlinear regime at lower values of the fluctuations. We successfully capture this nonlinear rheology by a mean-field model that describes the tissue in terms of cell elongation and cell rearrangements. We furthermore introduce anisotropic active stresses in the vertex model and analyze their effect on rheology. We include this anisotropy in the mean-field model and show that it recapitulates the behavior observed in the simulations. Our work clarifies how tissue rheology is related to stochastic cell rearrangements and provides a simple biophysical model to describe biological tissues. Further, it highlights the importance of nonlinearities when discussing tissue mechanics.

cond-mat.soft↗
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↗
arXiv2016

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

q-bio.CB↗
arXiv2013

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.

q-bio.CB↗
arXiv2012

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.

physics.bio-ph↗
arXiv2006

Measurement of FLux Fluctuations in Diffusion in the Small-Numbers Limit

Using a microfluidics device filled with a colloidal suspension of microspheres, we test the laws of diffusion in the limit of small particle numbers. Our focus is not just on average properties such as the mean flux, but rather on the features of the entire distribution of allowed microscopic trajectories that are possible during diffusive dynamics. The experiments show that: (1) the flux distribution is Gaussian; (2) Fick's Law --- that the average flux is proportional to the particle gradient --- holds even for particle gradients down to one or zero particles; (3) the variance in the flux is proportional to the sum of the particle numbers; and (4) there are backwards flows, where particles flow up a concentration gradient, rather than down it, and their numbers are well-predicted by theory and consistent with a new Flux Fluctuation Theorem.

cond-mat.stat-mech↗
arXiv2005

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.

cond-mat.stat-mech↗
arXiv2005

Dynamics of DNA Ejection From Bacteriophage

The ejection of DNA from a bacterial virus (``phage'') into its host cell is a biologically important example of the translocation of a macromolecular chain along its length through a membrane. The simplest mechanism for this motion is diffusion, but in the case of phage ejection a significant driving force derives from the high degree of stress to which the DNA is subjected in the viral capsid. The translocation is further sped up by the ratcheting and entropic forces associated with proteins that bind to the viral DNA in the host cell cytoplasm. We formulate a generalized diffusion equation that includes these various pushing and pulling effects and make estimates of the corresponding speed-ups in the overall translocation process. Stress in the capsid is the dominant factor throughout early ejection, with the pull due to binding particles taking over at later stages. Confinement effects are also investigated, in the case where the phage injects its DNA into a volume comparable to the capsid size. Our results suggest a series of in vitro experiments involving the ejection of DNA into vesicles filled with varying amounts of binding proteins from phage whose state of stress is controlled by ambient salt conditions or by tuning genome length.

q-bio.BM↗
arXiv2005

The effect of genome length on ejection forces in bacteriophage lambda

A variety of viruses tightly pack their genetic material into protein capsids that are barely large enough to enclose the genome. In particular, in bacteriophages, forces as high as 60 pN are encountered during packaging and ejection, produced by DNA bending elasticity and self-interactions. The high forces are believed to be important for the ejection process, though the extent of their involvement is not yet clear. As a result, there is a need for quantitative models and experiments that reveal the nature of the forces relevant to DNA ejection. Here we report measurements of the ejection forces for two different mutants of bacteriophage lambda, lambda b221cI26 and lambda cI60, which differ in genome length by ~30%. As expected for a force-driven ejection mechanism, the osmotic pressure at which DNA release is completely inhibited varies with the genome length: we find inhibition pressures of 15 atm and 25 atm, respectively, values that are in agreement with our theoretical calculations.

q-bio.BM↗
arXiv2004

Forces During Bacteriophage DNA Packaging and Ejection

The conjunction of insights from structural biology, solution biochemistry, genetics and single molecule biophysics has provided a renewed impetus for the construction of quantitative models of biological processes. One area that has been a beneficiary of these experimental techniques is the study of viruses. In this paper we describe how the insights obtained from such experiments can be utilized to construct physical models of processes in the viral life cycle. We focus on dsDNA bacteriophages and show that the bending elasticity of DNA and its electrostatics in solution can be combined to determine the forces experienced during packaging and ejection of the viral genome. Furthermore, we quantitatively analyze the effect of fluid viscosity and capsid expansion on the forces experienced during packaging. Finally, we present a model for DNA ejection from bacteriophages based on the hypothesis that the energy stored in the tightly packed genome within the capsid leads to its forceful ejection. The predictions of our model can be tested through experiments in vitro where DNA ejection is inhibited by the application of external osmotic pressure.

q-bio.BM↗