Coherent Timescales and Mechanical Structure of Multi-Cellular Aggregates

Abstract

3D cellular aggregates are a broadly studied model system for biological processes including morphogenesis, carcinogenesis, malignant invasion, wound healing, and tissue engineering. Tissue-like aggregates are well known to exhibit liquid-like behavior in the long-times (hours), particularly manifesting a “surface tension” analogous to liquids. On the other hand, the mechanical behavior in the short times (seconds to minutes) is very different and has received less attention. The current work uses shape relaxation experiments to investigate the structural characteristics of aggregates in the short times. Two coherent timescales are observed, one on the order of seconds; the other, tens of seconds. Both are found to be persistent across all examined cell types (GBM, 3T3, Rat2, L-cells) despite drastic changes in other properties such as tissue surface tension (by two orders of magnitude) and adhesion strength. A precise mathematical theory previously developed is used to extract the viscoelastic properties of aggregates from the measured timescales. The analysis suggests that aggregates are a composite of an unusually “soft” interior (weak bulk elastic modulus) enclosed by a relatively stiffer envelope. Additionally, aggregate surface tension, elastic modulus, and viscosity observe proportionality. This result suggests that the underlying cellular properties are regulated in a precise manner. The root-cause for multi-cellular aggregation to preserve such timescales requires further investigation.