Hybrid Markov-mass action law model for cell activation by rare binding events: Application to calcium induced vesicular release at neuronal synapses
Open accessAbstract
Binding of molecules, ions or proteins to small target sites is a generic step of cell activation. This process relies on rare stochastic events where a particle located in a large bulk has to find small and often hidden targets. We present here a hybrid discrete-continuum model that takes into account a stochastic regime governed by rare events and a continuous regime in the bulk. The rare discrete binding events are modeled by a Markov chain for the encounter of small targets by few Brownian particles, for which the arrival time is Poissonian. The large ensemble of particles is described by mass action laws. We use this novel model to predict the time distribution of vesicular release at neuronal synapses. Vesicular release is triggered by the binding of few calcium ions that can originate either from the synaptic bulk or from the entry through calcium channels. We report here that the distribution of release time is bimodal although it is triggered by a single fast action potential. While the first peak follows a stimulation, the second corresponds to the random arrival over much longer time of ions located in the synaptic terminal to small binding vesicular targets. To conclude, the present multiscale stochastic modeling approach allows studying cellular events based on integrating discrete molecular events over several time scales.
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- Authors
- Guerrier, C., & Holcman, D.
- Affiliations
- École Normale Supérieure - PSL (FR)
- University of Cambridge (GB)
- Corresponding author
- Holcman, David
- Venue
- Scientific Reports
- Published
- 2016-10-18
- Volume
- 6
- Issue
- 1
- Pages
- 35506-35506
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC5067597
- OpenAlex
- W2539404277
- Cited by
- 16
- References
- 34
- Citations by year
- 2026: 2 · 2023: 1 · 2022: 3 · 2021: 1 · 2019: 3 · 2018: 3 · 2017: 3
- FWCI
- 1.70
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- HAL (submittedVersion, other-oa)
- Topics
- Physical Sciences › Physics and Astronomy › Statistical and Nonlinear Physics › stochastic dynamics and bifurcation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Diffusion and Search Dynamics
- Keywords
- Brownian particles, synaptic vesicle release, synapses, calcium channels, cell activation
- MeSH terms
- Calcium, Computer Simulation, Markov Chains, Models, Neurological, Neurons, Synaptic Vesicles, Time Factors, Presynaptic Terminals, Biophysical Phenomena
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