Beyond bulk physics: interfacial and confinement effects in aqueous microdroplets

Aqueous microdroplets provide a mesoscopic platform for investigating aqueous solutions under finite confinement. Despite their compositional diversity, including emulsions, vesicles, biomolecular condensates, synthetic cells, and living cells, these systems share a common physical setting defined by finite volume and a high surface-to-volume ratio, through which interfaces become dynamically coupled to the confined interior. At these length scales, neither molecular descriptions nor macroscopic continuum theories can fully describe confined aqueous systems, and concepts and measurement strategies developed for bulk solutions cannot always be applied directly. This review presents a physics-based framework for understanding how confinement and interfaces influence experimentally accessible physical observables, including mechanics, molecular transport, partitioning, electrostatic interactions, and phase behavior. Rather than organizing the literature by material systems, we focus on how to interpret these observables, summarize representative experimental approaches along with their physical assumptions and limitations, and discuss how finite confinement influences measurement interpretation and the applicability of bulk theoretical frameworks. By highlighting shared physical characteristics across diverse aqueous microdroplet systems, this review provides a conceptual bridge between traditional bulk studies and confined aqueous solutions. We conclude by discussing future challenges toward establishing a quantitative framework that consistently incorporates interfaces, finite confinement, and finite-size effects in synthetic and biological compartments.