Complexity of matrix phenotypes

The extracellular matrix is engaged in an ever-evolving and elegant ballet of dynamic reciprocity that directly and bi-directionally regulates cell behavior. Homeostatic and pathophysiological changes in cell-matrix signaling cascades manifest as complex matrix phenotypes. Indeed, the extracellular matrix can be implicated in virtually every known human disease, thus, making it the most critical and dynamic “organ” in the human body. The overall goal of this Special Issue is to provide an accurate and inclusive functional definition that addresses the inherent complexity of matrix phenotypes. This goal is summarily achieved via a corpus of expertly written articles, reviews and original research, focused at answering this question empirically and fundamentally via state-of-the-art methods and research strategies. •ECM is the most important “organ” of the body; virtually all pathologies emanate from aberrant cell-matrix interactions•Matrix phenotypes manifest from ECM molecules and signaling into the cell nucleus as a form of “dynamic reciprocity”•This review focuses on the complexity of matrix phenotypes as diverse as the extracellular matrix itself•State-of-the-art methods, from ex vivo to next generation “omics” assays, bring intricate matrix phenotypes into focus•Deciphering the complexity of matrix phenotypes will uncover novel therapeutics and biomarkers to diagnose and treat disease