ReGuCel

The microenvironment is the immediate small-scale environment surrounding a cell that critically influences cellular behaviour through biochemical and biophysical cues. These cues rearrange across time and space to drive the sequential molecular events required by intricate multicellular processes, such as throughout embryogenesis and wound healing. However, the complexity of evolving microenvironments hinders our understanding of these important processes under user-defined conditions (in vitro). Our main limitation is the absence of methodologies capable of generating environments that can co-evolve with the cells by reciprocal communication. To solve this limitation, ReGuCel will establish reactive microenvironments: DNA-regulated media that will sense the state of the cell and trigger a pertinent response over cellular behaviour. My team will exploit the features of DNA molecular programming to attain three key objectives: 1) the development of in situ biosensors to characterize the state of the cell, 2) the implementation of programmable actuation mechanisms to control cellular behaviour, 3) the constitution of reactive microenvironments capable of autonomously guiding cellular wound healing outcomes from adverse conditions. These ambitious objectives demand computing, multiplexing and out-of-equilibrium properties, all of which can be granted by DNA molecular programs to operationalize reactive microenvironments. The interdisciplinarity of this project is reflected in the necessity of interweaving DNA nanotechnology, chemistry and cell biology. The immediate gains include the creation of live cellular profiling, autonomous and sequential in vitro cell signalling, and co-evolving microenvironments for the study of dynamic multicellular processes. In the long run, changing the dogma of static in vitro cultures will open new avenues for the development of dynamic therapies and spark evolutionary tissue engineering.