Homeostatic artificial cells enable self-protection in prototissue spheroids

Abstract

Prototissues made from artificial cells (ACs) aim to replicate the behaviors of living tissues, such as communication, collective behavior, and homeostasis. Despite progress in developing diverse AC types, building prototissues and achieving effective communication as well as collective behavior in such prototissues remain challenging. We introduce ACs with an intrinsic homeostatic pH control mechanism that can be organized into prototissues to collectively maintain a stable microenvironment and protect cargo from environmental pH fluctuations. These ACs contain pH-modulating enzymes within a pH-sensitive membrane, allowing for self-regulation through chemo-structural feedback. They adjust pH by importing substrates within a specific pH range and self-regulate to control substrate influx. This enables them to modulate local pH, manage cargo release, and facilitate interactive communication in organized spheroids. Our findings demonstrate the potential of homeostatic ACs to create advanced synthetic tissue mimics, replicating protective and communicative functions of living tissues for biomedical and tissue engineering applications.