Instructional materials that control cellular activity through synthetic Notch receptors

The field of regenerative engineering relies primarily on the dual technical platforms of cell selection/conditioning and biomaterial fabrication to support directed cell differentiation. As the field has matured, an appreciation for the influence of biomaterials on cell behaviors has resulted in engineered matrices that meet biomechanical and biochemical demands of target pathologies. Yet, despite advances in methods to produce designer matrices, regenerative engineers remain unable to reliably orchestrate behaviors of therapeutic cells in situ. Here, we present a platform named MATRIX whereby cellular responses to biomaterials can be custom defined by combining engineered materials with cells expressing cognate synthetic biology control modules. Such privileged channels of material-to-cell communication can activate synthetic Notch receptors and govern activities as diverse as transcriptome engineering, inflammation attenuation, and pluripotent stem cell differentiation, all in response to materials decorated with otherwise bioinert ligands. Further, we show that engineered cellular behaviors are confined to programmed biomaterial surfaces, highlighting the potential to use this platform to spatially organize cellular responses to bulk, soluble factors. This integrated approach of coengineering cells and biomaterials for orthogonal interactions opens new avenues for reproducible control of cell-based therapies and tissue replacements.

Automated summary

The field of regenerative engineering relies on cell selection/conditioning and biomaterial fabrication to direct cell differentiation. The MATRIX platform has been developed to enable custom-defined cellular responses to biomaterials by combining engineered materials with cells expressing synthetic biology control modules. This approach allows for the activation of synthetic Notch receptors and the control of various cellular activities in response to otherwise bioinert ligands, offering new possibilities for reproducibly controlling cell-based therapies and tissue replacements.