Team:MIT

Tissues by Design

Our project focuses on tissue self-construction to achieve specific patterns of cell differentiation (initially with fluorescence, ultimately with cell fate regulators) with genetic circuits. To accomplish this, we focused on three components: cell-cell communication pathways, intracellular information processing circuits, and cell-cell adhesion. Through engineered control of these mechanisms, we are investigating how programmed local rules of interactions between cells can lead to the emergence of desired global patternings.

Above is the result of a simulation run, starting with undifferentiated cells and ending with a pattern.

Specifically, we've developed a modular juxtacrine cell-cell signaling platform, using Notch and Delta proteins. Below(left) is a simulation of pattern formation of cells with different genetic circuits. Below(right) is an animation depicting showing the Notch-Delta interaction leading to the cleavage of the Notch intracellular domain, which enters the nucleus and leads to the expression of cadherins, which cause cells to adhere to similarly expressing cells.