Paper List
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Formation of Artificial Neural Assemblies by Biologically Plausible Inhibition Mechanisms
This work addresses the core limitation of the Assembly Calculus model—its fixed-size, biologically implausible k-WTA selection process—by introducing...
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How to make the most of your masked language model for protein engineering
This paper addresses the critical bottleneck of efficiently sampling high-quality, diverse protein sequences from Masked Language Models (MLMs) for pr...
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Module control in youth symptom networks across COVID-19
This paper addresses the core challenge of distinguishing whether a prolonged societal stressor (COVID-19) fundamentally reorganizes the architecture ...
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JEDI: Jointly Embedded Inference of Neural Dynamics
This paper addresses the core challenge of inferring context-dependent neural dynamics from noisy, high-dimensional recordings using a single unified ...
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ATP Level and Phosphorylation Free Energy Regulate Trigger-Wave Speed and Critical Nucleus Size in Cellular Biochemical Systems
This work addresses the core challenge of quantitatively predicting how the cellular energy state (ATP level and phosphorylation free energy) governs ...
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Packaging Jupyter notebooks as installable desktop apps using LabConstrictor
This paper addresses the core pain point of ensuring Jupyter notebook reproducibility and accessibility across different computing environments, parti...
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SNPgen: Phenotype-Supervised Genotype Representation and Synthetic Data Generation via Latent Diffusion
This paper addresses the core challenge of generating privacy-preserving synthetic genotype data that maintains both statistical fidelity and downstre...
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Continuous Diffusion Transformers for Designing Synthetic Regulatory Elements
This paper addresses the challenge of efficiently generating novel, cell-type-specific regulatory DNA sequences with high predicted activity while min...
ATP Level and Phosphorylation Free Energy Regulate Trigger-Wave Speed and Critical Nucleus Size in Cellular Biochemical Systems
School of Physics, Center for Quantitative Biology, Peking University, Beijing 100871, China
30秒速读
IN SHORT: This work addresses the core challenge of quantitatively predicting how the cellular energy state (ATP level and phosphorylation free energy) governs the speed, direction, and critical initiation size of propagating biochemical trigger waves.
核心创新
- Methodology Develops a thermodynamically consistent reaction-diffusion framework that treats ATP concentration ([ATP]) and the nonequilibrium parameter γ (=[ATP]/(Keq[ADP][Pi])) as independent control variables for analyzing trigger waves.
- Biology Identifies the intracellular energetic state as a direct regulator of trigger-wave behavior, quantitatively linking metabolic conditions (ATP/ADP/Pi ratio) to spatiotemporal propagation dynamics.
- Theory Derives analytical expressions showing that the critical excitation radius (Rc) for sustained wave propagation depends on both [ATP] and γ, with scaling Rc ∝ 1/√[ATP] under specific approximations.
主要结论
- ATP concentration ([ATP]) and the phosphorylation free energy parameter (γ) jointly regulate trigger-wave speed (c0), with a dominant scaling c0 ∝ √[ATP] in the forward propagation regime.
- The sign of the potential difference (ΔF) between bistable states, determined by [ATP] and γ, dictates wave propagation direction (forward for ΔF<0, reverse for ΔF>0), with a stationary interface at ΔF=0.
- The critical nucleus radius (Rc) for sustained spherical wave propagation is inversely related to wave speed (Rc = D(d-1)/c0), leading to the prediction that higher [ATP] reduces the minimum trigger size required (Rc ∝ 1/√[ATP]).
摘要: Trigger waves are self-regenerating propagating fronts that emerge from the coupling of nonlinear reaction kinetics and diffusion. In cells, trigger waves coordinate large-scale processes such as mitotic entry and stress responses. Although the roles of circuit topology and feedback architecture in generating bistability are well established, how nonequilibrium energetic driving shapes wave propagation is less well understood. Here, we employ a thermodynamically consistent reaction–diffusion framework to investigate trigger-wave dynamics in ATP-dependent phosphorylation–dephosphorylation systems. We first recapitulate general expressions for trigger-wave speed in the bistable regime and analyze curvature-induced corrections that determine the minimum critical nucleus required for sustained propagation in higher dimensions. We then apply this framework to two representative systems, treating ATP concentration and the nonequilibrium parameter γ=[ATP]/(Keq[ADP][Pi]) as independent control variables to examine how energetic driving regulates wave propagation. Our results show that ATP and γ not only modulate wave speed, but can also reverse the direction of propagation and reshape the parameter regime supporting trigger waves. The critical excitation radius also depends on both ATP concentration and phosphorylation free energy. These findings identify the intracellular energetic state as a regulator of trigger-wave behavior, linking metabolic conditions to the spatial dynamics of wave propagation. More broadly, this framework connects classical reaction–diffusion theory with ATP-driven biochemical regulation and provides a general perspective on related energy-dependent cellular decision-making processes.