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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

Nutrient shielding in clusters of cells.

Maxim O Lavrentovich¹, John H Koschwanez, David R Nelson

¹Department of Physics, Harvard University, Cambridge, Massachusetts 02138, USA.

Physical Review. E, Statistical, Nonlinear, and Soft Matter Physics

|July 16, 2013

Summary

Cellular nutrient shielding in colonies limits growth. A new theory predicts the nutrient-rich outer shell thickness (ℓ) based on cell absorption strength (ν), volume fraction (φ), and nutrient concentration (ψ(∞)).

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Preparation of Neuronal Co-cultures with Single Cell Precision

Preparation of Neuronal Co-cultures with Single Cell Precision

Published on: May 20, 2014

Area of Science:

Cellular and Molecular Biology
Biophysics
Mathematical Biology

Background:

Cellular nutrient consumption depends on uptake kinetics and spatial arrangement.
Large cell clusters exhibit inhibited growth at the center due to nutrient shielding by outer cells.

Purpose of the Study:

To develop an effective medium theory predicting the thickness of the nutrient-receiving outer shell of cell clusters.
To identify key parameters influencing nutrient penetration and growth within cell colonies.

Main Methods:

Developed an effective medium theory treating cells as partially absorbing spherical nutrient sinks.
Introduced a dimensionless parameter (ν) for cell absorption strength.
Compared theoretical predictions with numerical simulations and experimental data from yeast colonies.

Main Results:

The theory predicts a nutrient-receiving shell thickness (ℓ) within cell clusters.
Shell thickness (ℓ) decreases with increasing cell absorption strength (ν), cell volume fraction (φ), and decreasing ambient nutrient concentration (ψ(∞)).
Experimental validation using Saccharomyces cerevisiae colonies showed good agreement with theoretical predictions.

Conclusions:

The effective medium theory provides a robust framework for understanding nutrient diffusion and growth limitations in cell colonies.
The study quantifies the relationship between cellular properties, colony architecture, and nutrient availability.
Findings are applicable across diverse cell types, from microbes to human tissues.