Allometric scaling in-vitro

TL;DR

This paper develops a theoretical and computational framework to achieve quarter power allometric scaling in in-vitro tissue models, which could improve their physiological relevance and predictive power.

Contribution

It introduces a model for in-vitro allometric scaling based on oxygen diffusion and consumption, extending the concept beyond vascular tissues.

Findings

Physiological scaling maintained with 5-60% of tissue exposed to low oxygen levels.

Significant oxygen gradients occur in spherical tissue constructs with Thiele modulus 8-80.

Implications for designing physiologically relevant in-vitro systems.

Abstract

The quarter power allometric scaling of mammalian metabolic rate is largely regarded as a universal law of biology. However, it is well known that cell cultures do not obey this law. The current thinking is that were in-vitro cultures to obey quarter power scaling, they would have more predictive power and could for instance provide a viable substitute for animals in research. About two decades ago, West and coworkers established a model which predicts that metabolic rate follows a quarter power relationship with the mass of an organism, based on the premise that tissues are supplied nutrients through a fractal distribution network. This paper outlines a theoretical and computational framework for establishing quarter power scaling in-vitro, starting where fractal distribution ends. Allometric scaling in non-vascular spherical tissue constructs was assessed using models of Michaelis Menten oxygen consumption and diffusion. The results demonstrate that physiological scaling is maintained when about 5 to 60% of the construct is exposed to oxygen concentrations less than the Michaelis Menten constant. In these conditions the Thiele modulus is between 8 and 80, with a significant concentration gradient in the sphere. The results have important implications for the design of downscaled in-vitro systems with physiological relevance.