Light-activated signaling in DNA-encoded sender-receiver architectures

Abstract

AbstractCollective decision making by living cells is facilitated by exchange of diffusible signals where sender cells release a chemical signal that is interpreted by receiver cells. Biologists have started to unravel the underlying physicochemical determinants that control the effective communication distance using genetically modified cells. However, living systems are inherently challenging to manipulate and study systematically and quantitatively. Therefore, the development of generic and tunable abiotic mimics featuring compartmentalized signaling is highly desirable. Here, by adapting a previously reported artificial cell-cell communication system, we engineer DNA-encoded sender-receiver architectures, where protein-polymer microcapsules act as cell mimics and molecular communication occurs through diffusive DNA signals. We prepare spatial distributions of sender and receiver protocells using a microfluidic trapping array, and setup a signaling gradient from a single sender cell using light, which activates surrounding receivers through DNA strand displacement. Our systematic analysis reveals how the effective signal range of a single sender is determined by various factors including the density and permeability of receivers, extracellular signal degradation, signal consumption and catalytic regeneration. In addition, we construct a three-population configuration where two sender cells are embedded in a dense array of receivers that implement Boolean logic and investigate spatial integration of non-identical input cues. The results advance our understanding of diffusion-based sender-receiver topologies and present a strategy for constructing spatially controlled chemical communication systems that have the potential to reconstitute collective cellular behavior.