Volumetric compression for engineering living systems

Life, as a dense manifestation of soft matter, undergoes changes in water content, biomacromolecular concentrations, condensation and crowding due to volumetric compression. These molecular-level alterations in turn influence cell fate and function by modulating the kinetics and equilibria of biochemical reactions. Volumetric compression is a pervasive phenomenon in the human body, which manifests itself during development, limb movement, digestion, tumorigenesis and injury. Despite its ubiquity, it remains an underappreciated process compared with other biochemical and mechanical pathways. Nevertheless, the widespread effects of volumetric compression span across tissues, species and even kingdoms, which can be leveraged for regenerative, synthetic biology, biosensing and immunotherapeutic applications, among others. This Review provides an in-depth discussion of emerging engineering methods centred on volumetric compression, including foundational rationales, design principles and illustrative applications.