Chemomechanical regulation of growing tissues from a thermodynamically-consistent framework and its application to tumor spheroid growth.

Abstract

It is widely recognized that reciprocal interactions between cells and their microenvironment, via mechanical forces and biochemical signaling pathways, regulate cell behaviors during normal development, homeostasis and disease progression such as cancer. However, how exactly cells and tissues regulate growth in response to chemical and mechanical cues is still not clear. Here, we propose a framework for the chemomechanical regulation of growth based on thermodynamics of continua and growth-elasticity to predict growth patterns. Combining the elastic and chemical energies, we use an energy variational approach to derive a novel formulation that isolates the mass-conserving tissue rearrangement from the mass-accretion volumetric growth, and incorporates independent energy-dissipating stress relaxation and biochemomechanical regulation of the volumetric growth rate respectively. We validate the model using experimental data from growth of tumor spheroids in confined environments. We also investigate the influence of model parameters, including tissue rearrangement rate, tissue compressibility, strength of mechanical feedback and external mechanical stimuli, on the growth patterns of tumor spheroids.