Nanoscale Interfacial Organization Governs Maturation and Collapse in Passive versus Active Condensates

Peptide-based coacervates are model systems for membraneless organelles and protocells, which are central to understanding intracellular organization and the origins of life. However, their functions rely on nanoscale structural details and dynamics that are poorly understood. Using in situ liquid and cryogenic electron microscopy, optical imaging, and computational modeling, we show how nanoscale reorganization drives distinct behaviors in passive and active peptide condensates. Passive droplets form metastable multiphase intermediates with membrane-like interfaces that stabilize and promote ordering during aging. Under active driving forces, these interfaces destabilize, triggering spontaneous bursting. Simulations show that bursting occurs when interior chemical conversion outpaces membrane deactivation, causing a rapid collapse. These findings identify the nanoscale interfacial structure and stability as key determinants of condensate maturation and collapse, providing a framework for designing programmable protocells.