Bead Interaction Potential from Physical confinement signals regulate the organization of stem cells in three dimensions

a) The piece-wise interaction potential (in units of the effective thermal energy) is shown as a function of separation (in units of the bead diameter). For short distances, a constant force is used which yields a softer repulsion than the full Lennard-Jones interaction (shown as a dashed line). For intermediate distances, the Lennard-Jones potential is used which contains both a repulsive and an attractive component. At large distances the potential is truncated such that the beads have a finite attraction range. Simulations were carried out to understand the influence of cell-substrate (ɛcs) and cell-cell (ɛcc) interactions on embryonic stem cells growing within different levels of confinement. A simulation rendered with a χ (ɛcs/ɛcc) value of 0.1 (a) in 100 µm channels and (b) on a flat surface, revealing that with a low cell-substrate adhesion, cells are capable of aggregating in a spheroidal manner through purely diffusive means. When generated with a χ of 4, under (c) 100 µm and (d) flat conditions, cells demonstrate typical flat island morphology irrespective of the confinement1,-3.