How does an embedded spheroid affect the rigidity of extracellular matrix?

Abstract

In vitro collagen networks and in silico fiber network models are typically used to represent extracellular matrix in tissues. Such networks exhibit the phenomenon of strain-stiffening, or an increase in elastic modulus with increasing strain, both under isotropic expansion and shear. However, the deformations induced in an extracellular matrix environment in the presence of a cellular aggregate are more complex, due to the irregularity of the tissue-environment interface, the mechanisms of force transmission between the tissue and the environment, and the rheology of the tissue itself. Therefore, using a two-dimensional vertex model of a tissue coupled to a surrounding spring network model, both of which can undergo rigidity transitions, we investigate the effects of a cellular aggregate on the rigidity of its environment. We find that the network's rigidity transition alone is sensitive to tissue size, mechanical properties, and surface tension. This sensitivity can, in part, be analytically estimated using a mean-field constraint counting approach to arrive at an effective spring network coordination number to determine how the network rigidity transition location shifts in the presence of the tissue spheroid. Moreover, we find that it is energetically favorable to create a ring of high-tension boundary cells in the tissue spheroid as the spring network rigidifies, as opposed to creating a string of high-tension cells through the bulk. We also find that increasing interfacial tension of the tissue spheroid facilitates rigidity in the spring network. In sum, our numerical and analytical results help reveal the complex mechanical interplay between a tissue spheroid and its surrounding environment.