Getting the big picture of cell-matrix interactions: High-throughput biomaterial platforms and systems-level measurements.

Living cells interact with the extracellular matrix (ECM) in a complex and reciprocal manner. Much has been learned over the past few decades about cell-ECM interactions from targeted studies in which a specific matrix parameter (e.g. stiffness, adhesivity) has been varied across a few discrete values, or in which the level or activity of a protein is controlled in an isolated fashion. As the field moves forward, there is growing interest in addressing cell-matrix interactions from a perspective, which has spurred a new generation of matrix platforms capable of interrogating multiple ECM inputs in a combinatorial and parallelized fashion. Efforts are also actively underway to integrate specialized, synthetic ECM platforms with global measures of cell behaviors, including at the transcriptomic, proteomic and epigenomic levels. Here we review recent advances in both areas. We describe how new combinatorial ECM technologies are revealing unexpected crosstalk and nonlinearity in the relationship between cell phenotype and matrix properties. Similarly, efforts to integrate "omics" measurements with synthetic ECM platforms are illuminating how ECM properties can control cell biology in surprising and functionally important ways. We expect that advances in both areas will deepen the field's understanding of cell-ECM interactions and offer valuable insight into the design of biomaterials for specific biomedical applications.