# Prototissues: Assembly strategies, collective behaviors, and emerging applications

## TL;DR

This paper reviews prototissues, which are interconnected protocells that enable advanced biomimetic functions and have potential in biomedicine and materials science.

## Contribution

The paper introduces a dual-dimensional framework for understanding and designing prototissue systems.

## Key findings

- Prototissues enable collective behaviors through inter-protocell adhesion and spatial programming.
- Challenges include dynamic adhesion, scaling architectures, and improving signal transport.
- The framework supports the development of more adaptive and functional artificial life systems.

## Abstract

Recent advances in bottom-up synthetic biology have significantly expanded the ability to construct artificial life systems. While most efforts focus on building protocells, many biomimetic functions arise only when multiple units operate collectively. Prototissues, formed from interconnected protocell assemblies, provide a platform for such emergent behaviors and offer broad potential in biomedicine, biosensing, and smart materials. This review introduces a dual-dimensional framework for understanding prototissue design. The first dimension examines inter-protocell adhesion strategies that define molecular connectivity, and the second examines spatial programming approaches that organize protocells into functional architectures. On this basis, the review summarizes key collective behaviors enabled by these design principles and highlights how advances in materials chemistry, synthetic biology, and advanced manufacturing support the development of increasingly adaptive and functional prototissues. Major challenges remain, including achieving dynamic and selective adhesion, scaling spatial architectures while maintaining resolution, improving signal transport, and enhancing biological integration. The review outlines potential pathways to address these issues and to guide the development of prototissues with more sophisticated, life-like properties. Overall, the conceptual framework and insights presented here provide a foundation for the rational design of next-generation prototissues and advance bottom-up synthetic biology toward more complex artificial life systems.

Image 1

•Prototissues are synergistic protocells with advanced biomimetic functions.•They can achieve innovative solutions in science, biomedicine, and materials.•Collective intelligence technologies drive state-of-the-art development.•Existing challenges and future outlooks are carefully analyzed and summarized.•The insights and frameworks would advance more complex artificial life systems.

Prototissues are synergistic protocells with advanced biomimetic functions.

They can achieve innovative solutions in science, biomedicine, and materials.

Collective intelligence technologies drive state-of-the-art development.

Existing challenges and future outlooks are carefully analyzed and summarized.

The insights and frameworks would advance more complex artificial life systems.