Heavy Metal-Binding Peptide Phytochelatin Drives Membraneless Compartmentalization and Biomineral-Like Structures via Nanoparticle Formation within Condensates

Phytochelatin is a heavy metal-binding biogenic peptide found across different organisms that helps cells mitigate cytotoxicity by chelating metal ions. Yeasts produce phytochelatin to chelate intracellular cadmium and sequester it as cadmium metal sulfide nanoparticles. These nanoparticles were proposed to be stored within cytoplasmic microcompartments, although it remains unclear whether they are stored within membrane-bound or membraneless compartments. Here, we focused on the structure of phytochelatin and hypothesized that it can form membraneless compartments with positively charged biomolecules, which are capable of internal cadmium sulfide sequestration. Indeed, mixing phytochelatin with natural polysaccharide chitosan led to the instant formation of membraneless condensates. Moreover, Cd and S were preferentially accumulated within the condensates relative to other elements and CdS nanoparticles formed inside them. These nanoparticles exhibited crystalline features, with sizes of 2–3 nm and structures comparable to those of the CdS particles observed in cells, which predominantly correspond to the hawleyite structure. This study demonstrated that heavy metal-binding peptides can participate in the formation of membraneless compartments and internal sequestration of nanoparticles. Our findings further indicate a potential role of phytochelatin-based membraneless compartments in spatially controlled intracellular biomineralization and heavy metal sequestration for cellular detoxification, which remains to be explored in vivo.