Incomplete Cell Sorting Creates Engineerable Structures with Long-Term Stability

Jesse Tordoff,Matej Krajnc,Nicholas Walczak,Matthew Lima,Jacob Beal,Stanislav Shvartsman,Ron Weiss

doi:10.1016/j.xcrp.2020.100305

Abstract

Summary Adhesion-mediated cell sorting has long been considered an organizing principle in developmental biology. While most computational models have emphasized the dynamics of segregation to fully sorted structures, cell sorting can also generate a plethora of transient, incompletely sorted states. The timescale of such states in experimental systems is unclear: if they are long-lived, they can be harnessed by development or engineered in synthetic tissues. Here, we use experiments and computational modeling to demonstrate how such structures can be systematically designed by quantitative control of cell composition. By varying the number of highly adhesive and less adhesive cells in multicellular aggregates, we find the cell-type ratio and total cell count control pattern formation, with resulting structures maintained for several days. Our work takes a step toward mapping the design space of self-assembling structures in development and provides guidance to the emerging field of shape engineering with synthetic biology.

Highlights

While most computational models have emphasized the dynamics of segregation to fully sorted structures, cell sorting can generate a plethora of transient, incompletely sorted states
By varying the number of highly adhesive and less adhesive cells in multicellular aggregates, we find the cell-type ratio and total cell count control pattern formation, with resulting structures maintained for several days
To establish whether other biologically relevant patterns can be created using cell sorting between highly adhesive cells and less adhesive cells, we created aggregates composed of two cell types with different adhesive properties: HEK293FT (HEK) cells and CHO K1 (CHO) cells

Summary

Introduction

We present a systematic study of a range of structures that can be constructed using a ubiquitous tool for self-organization in animal development: cell sorting. The process by which mixtures of cell types can physically rearrange themselves into distinct populations, is driven by differences in tissue surface tension between populations of cells. Tissue surface tension is determined primarily by an interplay between cell-cell adhesion and cell cortex tension.[10,11] Complete cell sorting can result in a range of structure types, including an engulfed cluster of one cell type surrounded by another cell type, or total separation of two cell types to distinct sections.

Results

Discussion

Conclusion