Paper List
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Mapping of Lesion Images to Somatic Mutations
This paper addresses the critical bottleneck of delayed genetic analysis in cancer diagnosis by predicting a patient's full somatic mutation profile d...
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Reinventing Clinical Dialogue: Agentic Paradigms for LLM‑Enabled Healthcare Communication
This paper addresses the core challenge of transforming reactive, stateless LLMs into autonomous, reliable clinical dialogue agents capable of longitu...
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Binary Latent Protein Fitness Landscapes for Quantum Annealing Optimization
通过将序列映射到二元潜在空间进行基于QUBO的适应度优化,桥接蛋白质表示学习和组合优化。
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Controlling Fish Schools via Reinforcement Learning of Virtual Fish Movement
证明了无模型强化学习可以利用虚拟视觉刺激有效引导鱼群,克服了缺乏精确行为模型的问题。
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.