Long-range intercellular communication is essential for multicellular biological systems to regulate multiscale cell–cell interactions and maintain life. Growing evidence suggests that intercellular calcium waves (ICWs) act as a class of long-range signals that influence a broad spectrum of cellular functions and behaviors. Importantly, mechanical signals, ranging from single-molecule-scale to tissue-scale in vivo, can initiate and modulate ICWs in addition to relatively well-appreciated biochemical and bioelectrical signals. Despite these recent conceptual and experimental advances, the full nature of underpinning mechanotransduction mechanisms by which cells convert mechanical signals into ICW dynamics remains poorly understood. This review provides a systematic analysis of quantitative ICW dynamics around three main stages: initiation, propagation, and regeneration/relay. We highlight the landscape of upstream molecules and organelles that sense and respond to mechanical stimuli, including mechanosensitive membrane proteins and cytoskeletal machinery. We clarify the roles of downstream molecular networks that mediate signal release, spread, and amplification, including adenosine triphosphate (ATP) release, purinergic receptor activation, and gap junction (GJ) communication. Furthermore, we discuss the broad pathophysiological implications of ICWs, covering pathophysiological processes such as cancer metastasis, tissue repair, and developmental patterning. Finally, we summarize recent advances in optical imaging and artificial intelligence (AI)/machine learning (ML) technologies that reveal the precise spatial-temporal-functional dynamics of ICWs and ATP waves. By synthesizing these insights, we offer a comprehensive framework of ICW mechanobiology and propose new directions for mechano-therapeutic strategies in disease diagnosis, cancer immunotherapies, and drug discovery.
长程细胞间通讯是多细胞生物系统调控多尺度细胞间相互作用、维持生命活动的重要基础。越来越多的证据表明，细胞间钙波（ICWs）作为一类长程信号分子，广泛影响细胞功能与行为。值得注意的是，除相对明确的生化与生物电信号外，从单分子尺度到组织尺度的体内机械信号同样能够启动并调控ICWs。尽管近年来在概念与实验研究方面取得进展，细胞将机械信号转化为ICW动态的力传导机制本质仍未完全阐明。本综述围绕启动、传播、再生/中继三个主要阶段，对ICW定量动力学进行系统分析。我们重点解析感知机械刺激的上游分子与细胞器图谱，包括机械敏感膜蛋白与细胞骨架系统；阐明介导信号释放、扩散与放大的下游分子网络作用机制，涵盖三磷酸腺苷（ATP）释放、嘌呤能受体激活及间隙连接（GJ）通讯。此外，我们探讨ICWs在癌症转移、组织修复、发育模式等病理生理过程中的广泛影响。最后，我们总结光学成像与人工智能（AI）/机器学习（ML）技术的最新进展，这些技术揭示了ICWs与ATP波精确的时空功能动力学。通过整合这些发现，我们构建了ICW力学生物学的综合框架，并为疾病诊断、癌症免疫治疗及药物研发领域的力学治疗策略提出新方向。
肿瘤(癌症)患者之家