Boundary-bulk patterning in three-dimensional confluent cellular collectives

Abstract

Organoids are in vitro cellular collectives from which brain-like, or gut-like, or kidney-like structures emerge. To make quantitative predictions regarding the morphology and rheology of a cellular collective in its initial stages of development, we construct and study a three-dimensional vertex model. In such a model, the cells are represented as deformable polyhedrons with cells sharing faces such that there are no gaps between them, otherwise known as confluent. In a bulk model with periodic boundary conditions, we find a rigidity transition as a function of the target cell shape index s0 with a critical value s∗0=5.39±0.01. For a confluent cellular collective with a finite boundary, and in the presence of lateral extensile and in-plane, radial extensile deformations, we find significant boundary-bulk patterning that is one-cell layer thick. More specifically, for lateral extensile deformations, the cells in the bulk are much less aligned with the direction of the lateral deformation than the cells at the boundary. For in-plane, radial deformations, the cells in the bulk exhibit much less reorientation perpendicular to the radial direction than the cells at the boundary. In other words, for both deformations, the bulk cells are insulated from the deformations, at least over time scales much slower than the timescale for cellular rearrangements. Our results provide an underlying mechanism for some observed cell shape patterning in organoids. Finally, we discuss the use of a cellular-based approach to designing organoids with new types of morphologies to study the intricate relationship between structure and function at the multi-cellular scale.

Publication
arXiv:2204.07081 (Please contact me for access to the 3D Vertex Model C++ code. )
Tao Zhang
Tao Zhang
Special Research Fellow