Hijacking living cells with surface engineering for internet of Bio-Nano Things

Abstract

The Internet of Bio-Nano Things (IoBNT) promises to revolutionize healthcare by interfacing the cyber domain with living systems at unprecedented resolution. Realizing this vision hinges on the development of Bio-Nano Things (BNTs), i.e., functional nodes capable of sensing, actuation, and communications within biological environments. Existing BNT architectures, e.g., nanomaterial-based, biosynthetic, and passive molecular agents, face significant limitations, including toxicity, lack of autonomy, or metabolic burdens. This paper posits a fourth paradigm: transient hijacking of living cells via non-genetic cell surface engineering (NG-CSE) to enable living BNTs. NG-CSE allows for the precise, reversible functionalization of cell membranes with synthetic molecular machinery, reprogramming cellular functions and interactions without genomic modification. It uniquely combines the biocompatibility and agency of cells with the nanotechnology-enabled programmability, circumventing key risks of genetic engineering. We review the NG-CSE toolbox and explore the opportunities it unlocks for IoBNT, including programmable cell-cell communication, dynamic network topologies, and improved bio-cyber interfacing. We propose novel IoBNT architectures that leverage these capabilities, such as circulating sentinel networks exploiting cellular agency for liquid biopsy, and rationally designed, in vitro biocomputers exploiting interkingdom interactions. Finally, we introduce tractable mathematical frameworks and performance metrics for lifecycle degradation and agency-aware networking, providing a conceptual roadmap to guide future experimental validation and effective utilization of NG-CSE-enabled living BNTs within IoBNT.