Mechanical Modulation, Physiological Roles, and Imaging Innovations of Intercellular Calcium Waves in Living Systems.

Journal: Cancers
Published Date: May 31, 2025

Abstract

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.

Authors

  • Cole Mackey
    Department of Mechanical and Aerospace Engineering, Herbert Wertheim College of Engineering, University of Florida, Gainesville, FL 32611, USA.
  • Yuning Feng
    Department of Mechanical and Aerospace Engineering, Herbert Wertheim College of Engineering, University of Florida, Gainesville, FL 32611, USA.
  • Chenyu Liang
    Department of Mechanical and Aerospace Engineering, Herbert Wertheim College of Engineering, University of Florida, Gainesville, FL 32611, USA.
  • Angela Liang
    J. Crayton Pruitt Family Department of Biomedical Engineering, University of Florida, Gainesville, FL 32611, USA.
  • He Tian
    Institute of Microelectronics and Tsinghua National Laboratory for Information Science and Technology (TNList), Tsinghua University, Beijing 100084, China.
  • Om Prakash Narayan
    Department of Biomedical Engineering, Tufts University, Medford, MA, 02155, USA.
  • Jiawei Dong
    Zhejiang Key Laboratory of Excited-State Energy Conversion and Energy Storage, Department of Chemistry, Zhejiang University, Hangzhou 310058, China.
  • Yongchen Tai
    J. Crayton Pruitt Family Department of Biomedical Engineering, University of Florida, Gainesville, FL 32611, USA.
  • Jingzhou Hu
    Department of Computer and Information Science and Engineering, University of Florida, Gainesville, FL 32603, USA.
  • Yu Mu
    Institute of Neuroscience, State Key Laboratory of Neuroscience, Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, 320 Yue-Yang Road, Shanghai 200031, China. Electronic address: my@ion.ac.cn.
  • Quang Vo
    Department of Biology, University of Florida, Gainesville, FL 32611, USA.
  • Lizi Wu
    Department of Molecular Genetics and Microbiology, University of Florida, Gainesville, FL 32603, USA.
  • Dietmar Siemann
    University of Florida Health Cancer Center (UFHCC), Gainesville, FL 32610, USA.
  • Jing Pan
    College of Veterinary Medicine, Gansu Agricultural University, Lanzhou, China.
  • Xianrui Yang
    College of Dentistry, University of Florida, Gainesville, FL 32610, USA.
  • Kejun Huang
    Department of Computer and Information Science and Engineering, University of Florida, Gainesville, FL 32603, USA.
  • Thomas George
    University of Florida Health Cancer Center (UFHCC), Gainesville, FL 32610, USA.
  • Juan Guan
    School of Materials Science and Engineering, Beihang University, Beijing, 100191, P. R. China. juan.guan@buaa.edu.cn.
  • Xin Tang
    School of Science, Huazhong Agricultural University, Wuhan, Hubei province, China.

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