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 systems 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.

活细胞以复杂且互惠的方式与细胞外基质 (ECM) 相互作用。在过去的几十年里，从靶向研究中了解了很多关于细胞-ECM 相互作用的知识，其中特定的基质参数（例如刚度、粘附性）在几个离散值之间发生变化，或者蛋白质的水平或活性受到控制以孤立的方式。随着该领域的发展，人们对从系统解决细胞-基质相互作用的兴趣越来越大透视，这激发了能够以组合和并行方式询问多个 ECM 输入的新一代矩阵平台。正在积极努力将专门的、合成的 ECM 平台与细胞行为的全球测量相结合，包括在转录组、蛋白质组和表观基因组水平。在这里，我们回顾了这两个领域的最新进展。我们描述了新的组合 ECM 技术如何揭示细胞表型和基质特性之间关系中的意外串扰和非线性。同样，将“组学”测量与合成 ECM 平台相结合的努力正在阐明 ECM 特性如何以令人惊讶和功能重要的方式控制细胞生物学。