Confined self-propulsion of an isotropic active colloid

To spontaneously break their intrinsic symmetry and self-propel at the micron scale, isotropic active colloidal particles and droplets exploit the nonlinear convective transport of chemical solutes emitted/consumed at their surface by the surface-driven fluid flows generated by these solutes. Significant progress was recently made to understand the onset of self-propulsion and nonlinear dynamics. Yet, most models ignore a fundamental experimental feature, namely the spatial confinement of the colloid, and its effect on propulsion. In this work the self-propulsion of an isotropic colloid inside a capillary tube is investigated numerically. A flexible computational framework is proposed based on a finite-volume approach on adaptative octree grids and embedded boundary methods. This method is able to account for complex geometric confinement, the nonlinear coupling of chemical transport and flow fields, and the precise resolution of the surface boundary conditions, that drive the system's dynamics. Somewhat counterintuitively, spatial confinement promotes the colloid's spontaneous motion by reducing the minimum advection-to-diffusion ratio or Péclet number, ${Pe}$ , required to self-propel; furthermore, self-propulsion velocities are significantly modified as the colloid-to-capillary size ratio $\kappa$ is increased, reaching a maximum at fixed ${Pe}$ for an optimal confinement $0<\kappa <1$ . These properties stem from a fundamental change in the dominant chemical transport mechanism with respect to the unbounded problem: with diffusion now restricted in most directions by the confining walls, the excess solute is predominantly convected away downstream from the colloid, enhancing front-back concentration contrasts. These results are confirmed quantitatively using conservation arguments and lubrication analysis of the tightly confined limit, $\kappa \rightarrow 1$ .

3D confinement regulates stem cell fate

Biophysical properties of the cellular microenvironment, including stiffness and geometry, influence cell fate. Recent findings have implicated geometric confinement as an important regulator of cell fate determination. Our understanding of how mechanical signals direct cell fate is based primarily on two-dimensional (2D) studies. To investigate the role of confinement on stem cell fate in three-dimensional (3D) culture, we fabricated a single cell microwell culture platform and used it to investigate how niche volume and stiffness affect human mesenchymal stem cell (hMSC) fate. The viability and proliferation of hMSCs in confined 3D microniches were compared with the fate of unconfined cells in 2D culture. Physical confinement biased hMSC fate, and this influence was modulated by the niche volume and stiffness. The rate of cell death increased, and proliferation markedly decreased upon 3D confinement. We correlated the observed differences in hMSC fate to YES-associated protein (YAP) localization. In 3D microniches, hMSCs displayed primarily cytoplasmic YAP localization, indicating reduced mechanical activation upon confinement. These results demonstrate that 3D geometric confinement can be an important regulator of cell fate, and that confinement sensing is linked to canonical mechanotransduction pathways.

Morphodynamic signatures of MDA-MB-231 single cells and cell doublets undergoing invasion in confined microenvironments

Cancer cell metastasis is a major factor in cancer-related mortality. During the process of metastasis, cancer cells exhibit migratory phenotypes and invade through pores in the dense extracellular matrix. However, the characterization of morphological and subcellular features of cells in similar migratory phenotypes and the effects of geometric confinement on cell morphodynamics are not well understood. Here, we investigate the phenotypes of highly aggressive MDA-MB-231 cells in single cell and cell doublet (an initial and simplified collective state) forms in confined microenvironments. We group phenotypically similar single cells and cell doublets and characterize related morphological and subcellular features. We further detect two distinct migratory phenotypes, fluctuating and non-fluctuating, within the fast migrating single cell group. In addition, we demonstrate an increase in the number of protrusions formed at the leading edge of cells after invasion through geometric confinement. Finally, we track the short and long term effects of varied degrees of confinement on protrusion formation. Overall, our findings elucidate the underlying morphological and subcellular features associated with different single cell and cell doublet phenotypes and the impact of invasion through confined geometry on cell behavior.

Swelling of a granular hydrogel medium under confinement: individual and collective dynamic

The growth dynamics of polyacrylamide hydrogel beads due to liquid absorption under geometric confinement is studied. First, the behavior of individual hydrogel beads is investigated and, subsequently, the growth dynamics is analyzed in the presence of several interacting beads of the same material. In both, individual and collective studies, the magnitude of the geometric confinement is varied, in order to investigate the effect that the stress applied on the particles has on their hydration kinetics.