Enhanced extracellular matrix remodeling due to embedded spheroid fluidization.

Tumor spheroids are in vitro three-dimensional, cellular collectives consisting of cancerous cells. Embedding these spheroids in an in vitro fibrous environment, such as a collagen network, to mimic the extracellular matrix (ECM) provides an essential platform to quantitatively investigate the biophysical mechanisms leading to tumor invasion of the ECM. To understand the mechanical interplay between tumor spheroids and the ECM, we computationally construct and study a three-dimensional vertex model for a tumor spheroid that is mechanically coupled to a cross-linked network of fibers. In such a vertex model, cells are represented as deformable polyhedrons that share faces. Some fraction of the boundary faces of the tumor spheroid contain linker springs connecting the center of the boundary face to the nearest node in the fiber network. As these linker springs actively contract, the fiber network remodels. By toggling between fluid-like and solid-like spheroids via changing the dimensionless cell shape index, we find that the spheroid rheology affects the remodeling of the fiber network. More precisely, fluid-like spheroids displace the fiber network more on average near the vicinity of the spheroid than solid-like spheroids. We also find more densification of the fiber network near the spheroid for the fluid-like spheroids. These spheroid rheology-dependent effects are the result of cellular motility due to active cellular rearrangements that emerge over time in the fluid-like spheroids to generate spheroid shape fluctuations. Our results uncover intricate morphological-mechanical interplay between an embedded spheroid and its surrounding fiber network with both spheroid contractile strength and spheroid shape fluctuations playing important roles in the pre-invasion stages of tumor invasion.

Aggregate morphology of active Brownian particles on porous, circular walls.

We study the motility-induced aggregation of active Brownian particles (ABPs) on a porous, circular wall. We observe that the morphology of aggregated dense-phase on a static wall depends on the wall porosity, particle motility, and the radius of the circular wall. Our analysis reveals two morphologically distinct, dense aggregates; a connected dense cluster that spreads uniformly on the circular wall and a localized cluster that breaks the rotational symmetry of the system. These distinct morphological states are similar to the macroscopic structures observed in aggregates on planar, porous walls. We systematically analyze the parameter regimes where the different morphological states are observed. We further extend our analysis to motile circular rings. We show that the motile ring propels almost ballistically due to the force applied by the active particles when they form a localized cluster, whereas it moves diffusively when the active particles form a continuous cluster. This property demonstrates the possibility of extracting useful work from a system of ABPs, even without artificially breaking the rotational symmetry.