3D cell aggregates amplify diffusion signals.

Biophysical models can predict the behavior of cell cultures including 3D cell aggregates (3DCAs), thereby reducing the need for costly and time-consuming experiments. Specifically, mass transfer models enable studying the transport of nutrients, oxygen, signaling molecules, and drugs in 3DCA. These models require the defining of boundary conditions (BC) between the 3DCA and surrounding medium. However, accurately modeling the BC that relates the inner and outer boundary concentrations at the border between the 3DCA and the medium remains a challenge that this paper addresses using both theoretical and experimental methods. The provided biophysical analysis indicates that the concentration of molecules inside boundary is higher than that at the outer boundary, revealing an amplification factor that is confirmed by a particle-based simulator (PBS). Due to the amplification factor, the PBS confirms that when a 3DCA with a low concentration of target molecules is introduced to a culture medium with a higher concentration, the molecule concentration in the medium rapidly decreases. The theoretical model and PBS simulations were used to design a pilot experiment with liver spheroids as the 3DCA and glucose as the target molecule. Experimental results agree with the proposed theory and derived properties.
Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: K.PK., L.V., P.G. are employees of AstraZeneca and hold stock/stock options. This does not alter our adherence to PLOS ONE policies on sharing data and materials.
(Copyright: © 2024 Arjmandi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)