Pattern Formation in Engineered Bacteria: from Understanding to Applications

Patterns are ubiquitous in living organisms. However, the mechanisms driving self-organized pattern formations are not well understood. Due to the complexity of natural systems, many confounding factors complicate quantitative experiments and data interpretation, often making it difficult to draw definitive conclusions. Therefore, a limited number of experimental systems could enable precise perturbation and quantification of pattern formation. In comparison, the synthetic system serves as well-defined model systems to elucidate ‘‘design principles’’ of biological networks. In the past sixteen years, engineering pattern formation is a major endeavor in synthetic biology. However, there are only two studies about the generation of programmed self-organized pattern formation in growing cells based on coordinated dynamics in a population.

Intrigued by the challenge, my colleagues and I programmed E. coli with a synthetic gene circuit to generate self-organized pattern formation. Two implications of this engineered pattern-forming system were illustrated in my Ph.D. thesis.

First, the synthetic system provides a well-defined context to probe principles underlying the scaling property of self-organized pattern formation. Our mechanism underscores the importance of temporal control in generating scale-invariant patterns. The fundamental premise of this approach is that the principles defined in such engineered systems can be generally applicable to natural examples.

Second, the synthetic system serves as a foundation to generate structured materials with well-defined physical properties. Diverse natural biological systems can form structured materials with well-defined physical and chemical properties spontaneously. However, these natural processes are not readily programmable. By taking the synthetic biology approach, we demonstrate here the programmable, three-dimensional (3D) material fabrication using pattern-forming bacteria growing on top of permeable membranes as the structural scaffold. We equip the bacteria with an engineered protein that enables the assembly of gold nanoparticles into a hybrid organic-inorganic dome structure. The resulting hybrid structure functions as a pressure sensor that responds to touch. We show that the response dynamics are determined by the geometry of the structure, which is programmable by the membrane properties and the extent of circuit activation. Taking advantage of this property, we demonstrate signal sensing and processing using one or multiple bacterially assembled structures.