Cell-in-Shell Metacells in Single-Cell Nanoencapsulation.

Single-cell nanoencapsulation (SCNE) enables the direct integration of synthetic materials with living cells, forming cell-in-shell structures that augment native cellular functions without genetic modification. While SCNE has advanced applications in cytoprotection and cell-surface engineering, its full potential remains constrained by the absence of a unifying conceptual framework. In this Concept report, we introduce the term "metacells" to define a new class of engineered, living cell-in-shell systems endowed with dynamic functionality, environmental responsiveness, and programmable behavior. We propose that metacells are characterized by three core functional hallmarks-reconfigurability, loadability, and motility-which collectively distinguish them from conventional SCNE platforms. Through selected examples, we illustrate how these features enable metacells to sense and respond to external stimuli, carry and release functional payloads, and exhibit guided or autonomous motion. By establishing a foundational definition and organizing framework for metacells, this report provides a roadmap for future research at the intersection of materials science, synthetic biology, and cellular engineering, with implications for advanced therapeutics, microscale robotics, and interactive biohybrid systems.