Understanding complex reaction networks in space and time using microfluidics

Abstract

This talk describes our work to understand the robustness of two complex networks – human blood clotting and Drosophila early development. Complex networks of interacting reactions are responsible for the function and self-regulation of biological systems, and are the focus of a significant research effort. The spatiotemporal dynamics of such networks is especially interesting, but the complexity of these networks makes them difficult to understand and to synthetically reproduce. Haemostasis, a complex network of ~80 reactions, initiates localized blood clotting exclusively at the site of significant vascular injury, even when multiple patches of smaller damage are present throughout the vascular system. We have developed a simple experimental chemical system, built using a modular approach, that reproduces and predicts spatiotemporal dynamics of initiation and propagation of clotting in this complex network. Microfluidics was used to create in vitro environments that expose both the complex network (human blood plasma) and the model system to surfaces patterned with patches of clotting stimuli. As the model predicted, both systems displayed a threshold response with respect to patch size, with the magnitude of the threshold patch size described by the Damköhler number. These experiments show that blood can be exposed to significant amounts of clot-inducing stimuli, such as tissue factor, without initiating clotting. In our work with Drosophila, we perturb the environment around an embryo in both space and time to narrow the range of possible mechanisms for establishing robust development. Overall, our results demonstrate that chemical models, implemented and tested with microfluidics, may provide a framework for describing spatiotemporal dynamics and robustness of complex reaction networks.