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.

长期以来，粘附介导的细胞分选一直被认为是发育生物学的组织原则。尽管大多数计算模型都强调了分离到完全分类的结构的动态性，但细胞分类还可以生成大量的瞬态，不完全分类的状态。实验系统中此类状态的时间尺度尚不清楚：如果它们是长寿的，则可以通过开发或在合成组织中进行改造来利用它们。在这里，我们使用实验和计算模型来演示如何通过定量控制细胞组成来系统地设计此类结构。通过改变多细胞聚集体中高粘附力细胞和较少粘附细胞的数量，我们发现细胞类型比率和总细胞数控制模式形成，并保持了几天的结构。