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Nutrient Regulation by Continuous Feeding for Large-scale Expansion of Mammalian Cells in Spheroids

Nutrient Regulation by Continuous Feeding for Large-scale Expansion of Mammalian Cells in Spheroids

Published on: September 25, 2016

Understanding cellular growth strategies via optimal control.

Tommi Mononen¹, Teemu Kuosmanen¹, Johannes Cairns¹

¹Department of Computer Science, Organismal and Evolutionary Biology Research Programme, University of Helsinki, Helsinki 00014, Finland.

Journal of the Royal Society, Interface

|January 3, 2023

Summary

Optimal control theory helps predict and steer evolutionary adaptations in populations like microbes and cancer. This framework reveals how factors like experimental design can unintentionally shape evolutionary outcomes.

Keywords:

adaptive traits control theory experimental evolution microbes optimality

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Area of Science:

Evolutionary biology
Theoretical ecology
Microbial evolution

Background:

Evolutionary prediction and control are critical for managing rapidly adapting populations like cancer and microbes.
Understanding adaptation mechanisms is key to guiding these populations toward desired outcomes.

Purpose of the Study:

To introduce and apply a theoretical framework of optimal control for understanding adaptive trait usage.
To enable eco-evolutionarily informed population control strategies.
To model complex eco-evolutionary dynamics.

Main Methods:

Application of optimal control theory to adaptive metabolism and microbial experimental evolution.
Modeling demographic stochasticity and its effect on lag time evolution.
Incorporation of frequency-dependent selection into a state-dependent optimal control framework.

Main Results:

Demographic stochasticity alone can drive the evolution of lag times as an emergent property.
Experimental cycle length in serial transfer experiments can unintentionally select for specific growth strategies and lag times.
The framework successfully models complex eco-evolutionary dynamics, including frequency-dependent selection.

Conclusions:

Optimal control theory is a powerful tool for understanding organismal adaptations and cellular community decision-making.
The study highlights the importance of considering experimental design in evolutionary studies.
This approach offers insights into steering the evolution of populations with high adaptive potential.