局部细胞间耦合足以实现长距离钙信号传导
Local intercellular coupling is sufficient for long-range calcium signaling
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中文总结 AI 辅助
研究长距离细胞间钙信号传导机制，提出计算模型，表明相邻细胞局部耦合可在无快速分子扩散时产生和传播Ca2+振荡，再现实验空间影响范围，为相关疾病中局部基质硬化产生全身效应提供见解。
中文摘要 AI 辅助
长距离细胞间钙（Ca2+）信号传导协调从受精到收缩和细胞死亡等生物过程。经典模型将这种长距离传播归因于肌醇1,4,5-三磷酸（IP3）通过间隙连接的快速扩散。然而，最近有证据表明IP3扩散比以前认为的要慢得多，并且即使间隙连接被拆解，Ca2+振荡仍持续存在，这表明必须有另一种机制来维持长距离通信。在此，我们开发了一个计算模型，表明相邻细胞之间的局部耦合足以在没有快速分子扩散的情况下在细胞群体中产生和传播再生性Ca2+振荡。每个细胞被视为一个振荡器，其固有频率由其局部IP3浓度通过IP3依赖性不应期设定，相邻细胞使用Kuramoto最近邻框架进行耦合。在双刚度状态下，硬细胞外基质上的细胞带动其软基质邻居，产生Ca2+释放的偏移行波。这再现了实验观察到的有限空间影响范围（约8个细胞长度）。我们的发现提出了一种与扩散无关的钙信号传导范式，其中局部细胞间耦合驱动长距离通信，为哮喘和纤维化中局部细胞外基质硬化如何产生全身效应提供了见解。
英文摘要
Long-range intercellular calcium (Ca2+) signaling coordinates biological processes ranging from fertilization to contraction and cell death. The classical model attributes this long-range propagation to rapid diffusion of inositol 1,4,5-trisphosphate (IP3) through gap junctions. However, recent evidence that IP3 diffuses far more slowly than previously believed, and that Ca2+ oscillations persist even when gap junctions are disassembled, indicates that an alternative mechanism must sustain long-range communication. Here we develop a computational model showing that local coupling between neighboring cells is sufficient to generate and propagate regenerative Ca2+ oscillations across a cell population without fast molecular diffusion. Each cell is treated as an oscillator whose intrinsic frequency is set by its local IP3 concentration through an IP3-dependent refractory period, and neighboring cells are coupled using a Kuramoto nearest-neighbor framework. In a dual-stiffness regime, cells on a stiff extracellular matrix entrain their soft-matrix neighbors, producing an offset traveling wave of Ca2+ release. This reproduces the finite spatial range of influence (~8 cell lengths) observed experimentally. Our findings propose a diffusion-independent paradigm for calcium signaling in which local intercellular coupling drives long-range communication, offering insight into how localized ECM stiffening in asthma and fibrosis may produce systemic effects.
