Biology subjects

Kadiyala, U.

Publications and source records attributed to Kadiyala, U..

3 recordsLinked to original sources

bioRxiv2026

Energy-precision trade-off in mitotic oscillators revealed by ATP modulation in artificial cells

The temporal precision of biochemical oscillators is fundamentally constrained by the energy dissipated to suppress molecular fluctuations, a widely predicted trade-off governing information processing across biology and physics, from molecular motors to kinetic proofreading to computing. Yet, experimental validation in complex biological oscillators remains elusive due to challenges of systematically modulating energy while quantifying stochastic dynamics across large ensembles. Here, we establish a high-throughput droplet-microfluidics platform to reconstitute mitotic oscillations from Xenopus laevis egg extracts within thousands of sub-nanoliter compartments. By precisely tuning ATP across a broad free-energy landscape and developing an analytical framework that decouples intrinsic phase diffusion from quenched period heterogeneity, we uncover a hidden trade-off linking metabolic budget, oscillation speed, and precision. While speed peaks non-monotonically near physiological ATP levels and declines toward both high and low bifurcation limits, precision increases monotonically with energy. These findings provide direct experimental evidence that mitotic timing is actively shaped by energy budgets. Intriguingly, embryonic cell cycles are not optimized for maximum fidelity, but for a metabolic compromise maintaining just enough coherence for synchronous yet rapid divisions, placing the endogenous ATP budget near an energetic optimum balancing speed and accuracy. Our integrated artificial-cell and analytical strategy provides a generalizable framework for mapping thermodynamic limits in non-equilibrium biological dynamics.

biophysics↗

bioRxiv2024

Substrate Rigidity Modulates Segmentation Clock Dynamics in Isolated Presomitic Mesoderm Cells

The segmentation clock, a genetic oscillator in the presomitic mesoderm (PSM), is known to be influenced by biochemical signals, yet its potential regulation by mechanical cues remains unclear. The complex PSM microenvironment has made it challenging to isolate the effects of mechanical signals on clock behavior. Here we investigated how mechanical stimuli affect clock oscillations by culturing zebrafish PSM cells on bioengineered elastic substrates (PDMS micropost arrays) with tunable rigidities ranging from 0.6 to 1,200 kPa. We observed an inverse sigmoidal relationship between substrate rigidity and the percentage of oscillating PSM cells, with a switching rigidity threshold between 3-6 kPa. The oscillation periods of oscillating PSM cells showed a consistently broad distribution across the substrate rigidity conditions tested. Moreover, these oscillatory PSM cells exhibited distinct biophysical properties, including reduced motility, contractility, and sustained circularity, compared to non-oscillating ones. These findings highlight a role of cell-substrate interactions in regulating segmentation clock behavior, providing insights into the mechanobiology of somitogenesis. HighlightsO_LIOscillatory behaviors of single PSM cells respond to substrate rigidity in a switch-like manner, transitioning from an oscillatory state to a quiescent state at a critical rigidity threshold between 2.9 kPa and 6 kPa. C_LIO_LIIncreased substrate rigidity significantly suppresses the percentage of oscillating PSM cells, while oscillation period and cycle number show no consistent rigidity-dependent trend. C_LIO_LINon-oscillating PSM cells exhibit distinct biophysical properties compared to oscillating ones, including reduced circularity, a polarized and elongated morphology, greater motility, and increased contractility. C_LIO_LIAggregates of PSM cells exhibit similar trends in response to substrate rigidity changes, except for increased oscillation percentages across different rigidity conditions, suggesting a potential interplay between cell-cell and cell-matrix communications in influencing clock oscillation behavior. C_LI

developmental biology↗

bioRxiv2019

Anti-biofilm Activity of Graphene Quantum Dots via Self-Assembly with Bacterial Amyloid Proteins

Bacterial biofilms represent an essential part of Earths ecosystem that can cause multiple ecological, technological and health problems. The environmental resilience and sophisticated organization of biofilms are enabled by the extracellular matrix that creates a protective network of biomolecules around the bacterial community. Current anti-biofilm agents can interfere with extracellular matrix production but, being based on small molecules, are degraded by bacteria and rapidly diffuse away from biofilms. Both factors severely reduce their efficacy, while their toxicity to higher organisms create additional barriers to their practicality. In this paper we report on the ability of graphene quantum dots to effectively disperse mature Staphylococcus aureus biofilms, interfering with the self-assembly of amyloid fibers - a key structural component of the extracellular matrix. Mimicking peptide-binding biomolecules, graphene quantum dots form supramolecular complexes with phenol soluble modulins, the peptide monomers of amyloid fibers. Experimental and computational results show that graphene quantum dots efficiently dock near the N-terminus of the peptide and change the secondary structure of phenol soluble modulins, which disrupts their fibrillation and represents a novel strategy for mitigation of bacterial communities. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=117 SRC="FIGDIR/small/550285v1_ufig1.gif" ALT="Figure 1"> View larger version (17K): org.highwire.dtl.DTLVardef@a94402org.highwire.dtl.DTLVardef@b009b3org.highwire.dtl.DTLVardef@14cfb70org.highwire.dtl.DTLVardef@10f8e52_HPS_FORMAT_FIGEXP M_FIG GQD mediated staphylococcal biofilm dispersal. GQDs interact with PSM peptides and frustrate the fibrillation process. The reduction in amyloid fibers prevents robust stabilization of the biofilm. In addition, there is an increase in free monomeric and oligomeric PSM peptides which trigger dispersal events. C_FIG

bioengineering↗