Outside influences: The impact of extracellular matrix mechanics on cell migration

“No cell is an island” – highlights the interconnectedness of cellular behavior and the extracellular matrix (ECM). Cell migration is inherently contextual, as cells navigate and adapt to their environments, reshaping the ECM while being influenced by its properties. This review focuses on the mechanical characteristics of the ECM—specifically its architecture, porosity, dynamics, and stiffness—and how these attributes affect cell behavior and migration strategies. We discuss how the mechanical properties are modulated by the composition and arrangement of ECM components and the role of enzymatic activities, including crosslinking and matrix metalloproteinases. By presenting examples from vertebrate and invertebrate developmental models, we demonstrate how ECM mechanics dictate cell migration at various biological scales. Additionally, we examine the importance of cell-matrix adhesions in regulating migration speed and direction. While in vitro studies have advanced our understanding of the molecular mechanisms at play, significant questions persist regarding the regulation of cell migration by ECM mechanics in vivo. Ultimately, this synthesis aims to illuminate the complexities of cell-ECM mechanical interactions, pointing the way for future research that may unveil novel insights into how ECM mechanics influences cell migration during development and disease.