Mechano-metabolic control of multicellular morphogenesis

During multicellular morphogenesis, tissues display mechanical behaviors reminiscent of non-living materials. Unlike inert matter, however, tissues are not shaped solely by external forces; they self-assemble by generating - and adapting to - internal forces, a process that requires active catabolic (energetic) and anabolic (biosynthetic) metabolism. Crucially, tissue mechanics can in turn instruct metabolic states, revealing a reciprocal relationship. In this Review, we first examine the central role of metabolism in controlling the mechanics of diverse morphogenetic processes. Moving beyond the simplistic view of metabolism as a ubiquitous supplier of energy and biosynthetic precursors upstream of mechanics, we highlight instead its tight spatiotemporal regulation and specificity in shaping particular aspects of tissue mechanics. We also discuss evidence for mechanical regulation of metabolism and propose in vivo systems in which similar mechanisms may operate. By focusing on the very properties that distinguish living materials from inert ones, research into mechano-metabolic feedback loops during multicellular morphogenesis has the potential to drive major advances in our understanding of developmental biology.