Toward synthetic life—Emergence, growth, creation of offspring, decay, and rescue of fuel-dependent synthetic cells

<h2>Summary</h2> The <i>de novo</i> synthesis of life from non-living matter represents a bold scientific challenge, advancing our understanding of life's minimal requirements and offering revolutionary applications in biotechnology. We explore fuel-dependent synthetic cells based on complex coacervate droplets, which lack membranes and readily take up reactants. Given their fuel-dependent nature, these droplets emerge and grow when fuel is abundant but dissolve under starvation conditions, mimicking the non-equilibrium nature of life. However, their ability to produce offspring—a key requirement for life—has remained elusive. Moreover, their rescue in repetitive fueling-starvation experiments has not been demonstrated. Our work elucidates a mechanism of producing offspring by synthetic cells driven by solid-like speckles in droplets liberated as offspring. By fine-tuning parameters, we control offspring number and survival. Finally, refueling sustains second-generation synthetic cells. This system provides a platform for coupling offspring production with self-replicating molecules, paving the way for synthetic cells capable of Darwinian evolution.