Local intercellular coupling is sufficient for long-range calcium signaling
Abstract
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.
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BibTeX
@misc{goykadosh2026local,
title = {{Local intercellular coupling is sufficient for long-range calcium signaling}},
author = {Benjamin M. Goykadosh and Vasuretha Chandar and Harikrishnan Parameswaran},
howpublished = {arXiv},
year = {2026},
month = sep,
doi = {10.48550/arxiv.2607.21442},
eprint = {2607.21442},
archivePrefix = {arXiv},
url = {https://arxiv.org/abs/2607.21442},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - UNPB
TI - Local intercellular coupling is sufficient for long-range calcium signaling
AU - Benjamin M. Goykadosh
AU - Vasuretha Chandar
AU - Harikrishnan Parameswaran
PY - 2026
DA - 2026/09/16
PB - arXiv
DO - 10.48550/arxiv.2607.21442
UR - https://arxiv.org/abs/2607.21442
AB - 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.
ER -