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Breaking down calcium timing in heterogenous cells populations.
Alessandro Loppini1, Christian Cherubini2, Marta Bertolaso3
1Unit of Nonlinear Physics and Mathematical Modeling, Department of Engineering, Campus Bio-Medico University of Rome, Via A. del Portillo 21, 00128, Rome, Italy.
Bio Systems
|February 22, 2020
Summary
Cellular calcium signaling is crucial for biological functions. Mathematical models show how cell property changes can disrupt normal calcium dynamics, potentially leading to cancer initiation.
Area of Science:
- Cellular Biology
- Biophysics
- Mathematical Modeling
Background:
- Calcium signaling regulates diverse cellular processes including differentiation, apoptosis, mitosis, secretion, muscle contraction, and memory.
- The spatiotemporal dynamics of calcium signaling are critical for cellular and organ function, with cells acting as biological clocks that can synchronize.
- Heterogeneity in cellular properties can lead to emergent spatiotemporal dynamics.
Purpose of the Study:
- To investigate the impact of cellular property heterogeneity and pathological aggregates on calcium dynamics in hepatic non-excitable cell clusters.
- To analyze how variations in dysfunction severity and aggregate size influence calcium oscillations.
- To understand the generation of non-physiological calcium patterns due to dynamic interactions between cell clusters.
Main Methods:
- Utilized a mathematical model based on published experimental data for hepatic non-excitable cells.
- Simulated calcium dynamics in cell clusters comprising both normal and pathological cells.
- Varied the severity of cellular dysfunction and the size of pathological aggregates to observe effects on calcium oscillations.
Main Results:
- Strong and localized heterogeneity in cellular properties significantly alters organized calcium dynamics.
- Sub-populations of cells can develop their own coordinated dynamical organizations.
- Simulations revealed distinct cell behaviors related to intrinsic time signals and dynamic inter-cluster influences.
- Generated non-physiological yet organized calcium patterns through the interaction of differently behaving cell clusters.
Conclusions:
- Altered calcium dynamics resulting from cellular heterogeneity and pathological aggregates can lead to emergent, non-physiological patterns.
- These reorganized calcium activities may represent a potential precursor to cancer initiation.
- Understanding these complex calcium dynamics is crucial for deciphering cellular dysfunction and disease development.
