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Modeling Extracellular Vesicles-Mediated Interactions of Cells in the Tumor Microenvironment
Abstract:
Interactions of cells via extracellular vesicles (EVs) manipulate various actions, including cancer initiation and progression, inflammation, anti-tumor signaling and cell migration, proliferation and apoptosis in the tumor microenvironment. EVs as the external stimulus can activate or inhibit some receptor pathways in a way that amplify or attenuate a kind of particle release at target cells. This can also be carried out in a biological feedback-loop where the transmitter is affected by the induced release initiated by the target cell due to the EVs received from the donor cell, to create a bilateral process. In this paper, at first we derive the frequency response of internalization function in the framework of a unilateral communication link. This solution is adapted to a closed-loop system to find the frequency response of a bilateral system. The overall releases of the cells, given by the combination of the natural release and the induced release, are reported at the end of this paper and the results are compared in terms of distance between the cells and reaction rates of EVs at the cell membranes.
Insights
Cellular communication via extracellular vesicles (EVs) influences cancer and inflammation. This study models these interactions, revealing how EV signaling impacts cell behavior and release dynamics in biological feedback loops.
Area of Science:
- Cell biology
- Biophysics
- Systems biology
Background:
- Extracellular vesicles (EVs) mediate intercellular communication, influencing critical biological processes such as cancer progression, inflammation, and apoptosis.
- EVs act as external stimuli, modulating receptor pathways and particle release in target cells.
- This communication can form biological feedback loops, where donor and target cells influence each other's release rates.
Purpose of the Study:
- To mathematically model the frequency response of cellular internalization of EVs.
- To adapt the unilateral communication model to a closed-loop system for analyzing bilateral interactions.
- To investigate the impact of cell distance and EV reaction rates on overall cell release.
Main Methods:
- Derivation of the frequency response for an EV internalization function within a unilateral communication framework.
- Adaptation of the unilateral model to a closed-loop system to determine the frequency response of bilateral cell interactions.
- Analysis of overall cell release, combining natural and induced release mechanisms.
Main Results:
- The frequency response of the unilateral internalization function was successfully derived.
- The model was extended to accurately represent bilateral communication systems.
- Cellular release patterns were quantified and compared based on varying inter-cell distances and EV reaction kinetics.
Conclusions:
- The study provides a mathematical framework for understanding EV-mediated intercellular communication dynamics.
- The findings highlight the importance of spatial arrangement and reaction rates in modulating cellular responses to EVs.
- This work contributes to a deeper understanding of how EVs orchestrate complex biological processes within the tumor microenvironment.
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