Tracer particles sense local stresses in an evolving multicellular spheroid without affecting the anomalous dynamics of the cancer cells

TL;DR

This study demonstrates that inert tracer particles can accurately measure local stresses within a multicellular spheroid without disturbing the cancer cell dynamics, providing a reliable method for probing tumor microenvironments.

Contribution

The paper introduces a theoretical and simulation-based analysis showing tracer particles do not alter cancer cell stress distributions in spheroids, validating their use as stress reporters.

Findings

Tracer particles exhibit sub-diffusive and hyper-diffusive dynamics over different timescales.

Pressure profiles within spheroids are consistent with and without tracer particles.

Tracer particles do not significantly affect cancer cell behavior or stress measurements.

Abstract

Measurements of local stresses on the cancer cells (CCs), inferred by embedding inert compressible tracer particles (TPs) in a growing multicellular spheroid (MCS), show that pressure decreases monotonically as the distance from the core of the MCS increases. How faithfully do the TPs report the local stresses in the CCs is an important question because pressure buildup in the MCS is dynamically generated due to CC division, which implies that the CC dynamics should be minimally altered by the TPs. Here using theory and simulations, we show that although the TP dynamics is unusual, exhibiting sub-diffusive behavior on times less than the CC division times and hyper-diffusive dynamics on in the long-time limit, they do not affect the long-time CC dynamics or the local CC stress distributions. The CC pressure profile within the MCS, which decays from a high value at the core to the periphery, is almost identical with and without the TPs. That the TPs have insignificant effect on the local stresses in the MCS implies that they are reliable reporters of the CC microenvironment.