arXiv subjects

Parag Katira

Publications and source records attributed to Parag Katira.

6 recordsLinked to original sources

arXiv2025

Sequential binding-unbinding based specific interactions influence exchange dynamics and size distribution of protein condensates

The interaction lifetimes between condensate-forming biomolecules can dictate both the specificity of the condensate-forming species as well as the fluidity and exchange dynamics of these condensates. Using a heuristic modeling approach, we show that single-step vs. sequential, multistep binding-unbinding interactions between proteins can lead to similar average interaction lifetimes, but with either exponential or truncated power-law-like lifetime distributions, respectively. Combining this model with Brownian dynamics simulations, we find that the differences in these lifetime distributions influence the features of condensates, such as their fluidic nature, aging, and size distribution.

cond-mat.soft↗

arXiv2025

Kinesin-driven de-mixing of cytoskeleton composites drives emergent mechanical properties

The cytoskeleton is an active composite of filamentous proteins that dictates diverse mechanical properties and processes in eukaryotic cells by generating forces and autonomously restructuring itself. Enzymatic motors that act on the comprising filaments play key roles in this activity, driving spatiotemporally heterogeneous mechanical responses that are critical to cellular multifunctionality, but also render mechanical characterization challenging. Here, we couple optical tweezers microrheology and fluorescence microscopy with simulations and mathematical modeling to robustly characterize the mechanics of active composites of actin filaments and microtubules restructured by kinesin motors. We discover that composites exhibit a rich ensemble of force response behaviors, elastic, yielding, and stiffening, with their propensity and properties tuned by motor concentration and strain rate. Moreover, intermediate kinesin concentrations elicit emergent mechanical stiffness and resistance while higher and lower concentrations exhibit softer, more viscous dissipation. We further show that composites transition from well-mixed interpenetrating double-networks of actin and microtubules to de-mixed states of microtubule-rich aggregates surrounded by relatively undisturbed actin phases. It is this de-mixing that leads to the emergent mechanical response, offering an alternate route that composites can leverage to achieve enhanced stiffness through coupling of structure and mechanics.

cond-mat.soft↗

arXiv2023

Motor antagonism dictates emergent dynamics in active double networks tuned by crosslinkers

The cytoskeleton relies on diverse populations of motors, filaments, and binding proteins acting in concert to enable non-equilibrium processes ranging from mitosis to chemotaxis. Its versatile reconfigurability, programmed by interactions between its constituents, make the cytoskeleton foundational active matter. Yet, current active matter endeavors are limited largely to single force-generating components acting on a single substrate, far from the composite cytoskeleton in cells. Here, we engineer actin-microtubule double-networks, driven by kinesin and myosin motors and tuned by crosslinkers, to ballistically restructure and flow with speeds that span three orders of magnitude depending on the composite formulation and time relative to the onset of motor activity. Differential dynamic microscopy analyses reveal that kinesin and myosin compete to delay the onset of acceleration and suppress discrete restructuring events, while passive crosslinking of either actin or microtubules has an opposite effect. Our minimal advection-diffusion model and spatial correlation analyses correlate these dynamics to structure, with motor antagonism suppressing reconfiguration and de-mixing, while crosslinking enhances clustering. Despite the rich formulation space and emergent formulation-dependent structures, the non-equilibrium dynamics across all networks and timescales can be organized into three classes: slow isotropic reorientation, fast directional flow, and multimode restructuring. Moreover, our mathematical model demonstrates that diverse structural motifs can arise simply from the interplay between motor-driven advection and frictional drag. These general features of our platform facilitate applicability to other active matter systems, and shed light on diverse ways that cytoskeletal components can cooperate or compete to enable wide-ranging cellular processes.

physics.bio-ph↗

arXiv2022

Differences in cell death and division rules can alter tissue rigidity and fluidization

Tissue mechanical properties such as rigidity and fluidity, and changes in these properties driven by jamming-unjamming transitions (UJT), have come under recent highlight as mechanical markers of health and disease in various biological processes including cancer. However, most analysis of these mechanical properties and UJT have sidestepped the effect of cellular death and division in these systems. Cellular apoptosis (programmed cell death) and mitosis (cell division) can drive significant changes in tissue properties. The balance between the two is crucial in maintaining tissue function, and an imbalance between the two is seen in situations such as cancer progression, wound healing and necrosis. In this work we investigate the impact of cell death and division on tissue mechanical properties, by incorporating specific mechanosensitive triggers of cell death and division based on the size and geometry of the cell within in silico models of tissue dynamics. Specifically, we look at cell migration, tissue response to external stress, tissue extrusion propensity and self-organization of different cell types within the tissue, as a function of cell death and division and the rules that trigger these events. We find that not only do cell death and division events significantly alter tissue mechanics when compared to systems without these events, but that the choice of triggers driving these cell death and division events also alter the predicted tissue mechanics and overall system behavior.

cond-mat.soft↗

arXiv2022

Biophysical and Biochemical mechanisms underlying Collective Cell Migration in Cancer Metastasis

Multicellular collective migration is a ubiquitous strategy of cells to translocate spatially in diverse tissue environments to accomplish a wide variety of biological phenomena, viz. embryonic development, wound healing, and tumor progression. Diverse cellular functions and behaviors, for instance, cell protrusions, active contractions, cell-cell adhesion, biochemical signaling, remodeling of tissue micro-environment, etc., play their own role concomitantly to have a single concerted consequence of multicellular migration. Thus unveiling the driving principles, both biochemical and biophysical, of the inherently complex process of collective cell migration is an insurmountable task. Mathematical and computational models, in tandem with experimental data, help in shedding some light on it. Here we review different factors influencing Collective Cell Migration and then focus on different mathematical and computational models - discrete, hybrid, and continuum - which helps in revealing different aspects of multicellular migration. Finally, we discuss the applications of these modeling frameworks specific to cancer

q-bio.CB↗

arXiv2015

Yield Strength as a Thermodynamic Consequence of Information Erasure

We observe that the yield strength of a variety of materials, including highly structured and densely packed metals, alloys and semi-crystalline polymers is reasonably approximated by the thermal energy density of the material. This suggests that it is related to the entropic cost of the irreversible work done during plastic deformation rather than the enthalpic cost that depends on the elastic modulus of the material. Here we propose that the entropic cost of material rearrangement in crystalline solids arises from the difference in the uncertainty in building block positions before and after yielding and estimate it using Landauer's principle for information processing. The yield strength thus obtained in given by the thermal energy density of the material multiplied by ln(2) and provides a guidepost in estimating the strength of materials complementary to the "theoretical strength of solids".

cond-mat.mtrl-sci↗