Paper List
-
MCP-AI: Protocol-Driven Intelligence Framework for Autonomous Reasoning in Healthcare
This paper addresses the critical gap in healthcare AI systems that lack contextual reasoning, long-term state management, and verifiable workflows by...
-
Model Gateway: Model Management Platform for Model-Driven Drug Discovery
This paper addresses the critical bottleneck of fragmented, ad-hoc model management in pharmaceutical research by providing a centralized, scalable ML...
-
Tree Thinking in the Genomic Era: Unifying Models Across Cells, Populations, and Species
This paper addresses the fragmentation of tree-based inference methods across biological scales by identifying shared algorithmic principles and stati...
-
SSDLabeler: Realistic semi-synthetic data generation for multi-label artifact classification in EEG
This paper addresses the core challenge of training robust multi-label EEG artifact classifiers by overcoming the scarcity and limited diversity of ma...
-
Decoding Selective Auditory Attention to Musical Elements in Ecologically Valid Music Listening
This paper addresses the core challenge of objectively quantifying listeners' selective attention to specific musical components (e.g., vocals, drums,...
-
Physics-Guided Surrogate Modeling for Machine Learning–Driven DLD Design Optimization
This paper addresses the core bottleneck of translating microfluidic DLD devices from research prototypes to clinical applications by replacing weeks-...
-
Mechanistic Interpretability of Antibody Language Models Using SAEs
This work addresses the core challenge of achieving both interpretability and controllable generation in domain-specific protein language models, spec...
-
Fluctuating Environments Favor Extreme Dormancy Strategies and Penalize Intermediate Ones
This paper addresses the core challenge of determining how organisms should tune dormancy duration to match the temporal autocorrelation of their envi...
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.