Programmable Nanoarchitectonics for Artificial Cells via Coupled Multidimensional Regulation of Phase State and Multiscale Transport Dynamics

The rational design of functional artificial cells is limited by the inherent thermodynamic instability and uncontrolled coalescence of the simple liquid condensates. Here, a programmable artificial cell platform is established based on the complex coacervation of bovine serum albumin and poly(acrylic acid). The physical state, mesoscale fusion dynamics, and multiscale mass-transport properties of these compartments can be tailored through the coupled multidimensional regulation of intrinsic polymer chain length, stoichiometric ratios, and environmental buffer conditions. Specifically, polymer chain length modulates condensate morphology and internal mobility, stoichiometric ratio tunes fusion kinetics and terminal size, buffer-mediated interactions promote wetting changes, condensate densification, and solid-like arrest. Crucially, combining spatiotemporal tracking and fluorescence recovery after photobleaching (FRAP) reveals a nonparallel relationship between internal network mobility and long-term molecular accumulation. More dynamic coacervate networks facilitate rapid internal mobility but show limited long-term accumulation, whereas densely packed, buffer-collapsed networks restrict internal diffusion yet exhibit favorable partitioning and affinity that support enhanced long-term cargo retention. By transforming fluidic microreactors into efficient "molecular traps," this study provides a versatile framework for smart biomaterials and artificial cell-like compartmentalization platforms.