Polymeric encapsulation of bacterial biosensors enables co-culture with mammalian cells

Synthetic biology has enabled us to harness the ability of living systems to sense their environment and respond to changes to develop genetically-encoded biosensors for a variety of applications including biomanufacturing, healthcare, and as orthogonal control of cells. From a biomanufacturing standpoint, biosensors offer increased sensitivity and specificity for detection of key metabolites compared to traditional detection methods. However, one of the remaining challenges is whether the sensing elements should be placed inside the producing cells (which diverts cellular resources from bioproduction towards sensing) or whether dedicated biosensor cell populations could be created and cultured alongside the producer cells. In the latter case, the growth and division of the biosensor cells must be limited or they will overgrow the producer cells, leading to an overall loss of productivity from the culture. To tackle this challenge, we have been exploring strategies involving encapsulation of biosensor cells in materials that allow free diffusion of metabolites to the biosensor cells, but limit their growth within the culture.

In this talk, I will introduce LAMPS (Living Analytics in a Multilayer Polymer Shell) and demonstrate their application to the co-culture of a bacterial whole-cell biosensor for L-lactate with suspension-adapted mammalian cell lines producing a monoclonal antibody. LAMPS are composed of an inner layer of alginate containing the biosensor population, surrounded by one or more additional polymeric layers that prevent bacterial escape. Our results show that the biosensor population within LAMPS is able to sense L-lactate production by the mammalian producer cell lines and activate expression of a reporter gene in response. The response of the biosensor cells is proportional to the L-lactate acid concentration and the bacterial whole-cell biosensor does not escape the LAMPS to contaminate the cell culture.