Programming Self-Organizing Multicellular Shapes

The shapes made by living organisms have many properties that are desirable in materials engineering, including autonomous growth, adaptiveness to the environment, and self-healing. If we had the ability to regulate biological shape formation on a multicellular level, we could generate a new class of living materials that have the durability and self-organization of complex organisms. Towards this goal, we have built a system to programmably control the 3D shape and spatial patterning of multicellular aggregates. Our system includes CHO and HEK cell lines with engineered genetic circuits that can induce expression of different cadherins, which are common morphogenetic drivers in animal development. We found that, even when well mixed, populations of cells with different cadherin expression profiles sort themselves out in predictable ways. The resulting shapes vary significantly, including planes of semi-regular polka dots, a sphere engulfed by an outer shell, maze-like intertwined populations, and radial protrusions from a core. We can reliably select between these shapes and control their properties by changing the strength of cadherin expression, population ratio, cadherin identity, and total aggregate size. To predict and understand this behavior, we made a particle-based model of our system with differentially adhesive cell populations that can capture the range of shapes we generated. Using our data and model, we are working towards creating a high-level language for automated design that will allow a user to define a desired shape and output the appropriate experimental set up to achieve that shape. By creating a framework to programmably generate multicellular forms, this work will help establish the principles of synthetic morphogenesis and will provide a powerful new system to control living shapes.