The world today is experiencing new relations between natural, synthetic and digital worlds. Rather than considering these as materially distinct or ontologically separate, this Special Issue of Tsantsa interrogates how they are interlocked in socio-material processes of mediation, transmutation and valuation. Can the synthetic or digital be biologic and organic? What is natural about artificial materials and processes? By conceptualizing what distinguishes and connects different matters, the special issue moves beyond their essential qualities to make possible the comparison and commensuration of their relationships. Each contributor theorizes the social in the dis/connection between natural synthetics, the humanness of artificial intelligence, or the materiality of digital elements: in laboratories and gold refineries, with cyborg seeds and organic batteries, and through synthetic and digitally-produced human-like natural properties.