Paper List
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Nyxus: A Next Generation Image Feature Extraction Library for the Big Data and AI Era
This paper addresses the core pain point of efficiently extracting standardized, comparable features from massive (terabyte to petabyte-scale) biomedi...
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Topological Enhancement of Protein Kinetic Stability
This work addresses the long-standing puzzle of why knotted proteins exist by demonstrating that deep knots provide a functional advantage through enh...
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A Multi-Label Temporal Convolutional Framework for Transcription Factor Binding Characterization
This paper addresses the critical limitation of existing TF binding prediction methods that treat transcription factors as independent entities, faili...
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Social Distancing Equilibria in Games under Conventional SI Dynamics
This paper solves the core problem of proving the existence and uniqueness of Nash equilibria in finite-duration SI epidemic games, showing they are a...
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Binding Free Energies without Alchemy
This paper addresses the core bottleneck of computational expense in Absolute Binding Free Energy calculations by eliminating the need for numerous al...
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SHREC: A Spectral Embedding-Based Approach for Ab-Initio Reconstruction of Helical Molecules
This paper addresses the core bottleneck in cryo-EM helical reconstruction: eliminating the dependency on accurate initial symmetry parameter estimati...
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Budget-Sensitive Discovery Scoring: A Formally Verified Framework for Evaluating AI-Guided Scientific Selection
This paper addresses the critical gap in evaluating AI-guided scientific selection strategies under realistic budget constraints, where existing metri...
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Probabilistic Joint and Individual Variation Explained (ProJIVE) for Data Integration
This paper addresses the core challenge of accurately decomposing shared (joint) and dataset-specific (individual) sources of variation in multi-modal...
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.