Nano-Archaea Interfaces: From Single-Cell Mechanobiology to Functional Biohybrid Systems

The nano-bio interface, where nanomaterials and biological systems converge, represents a critical frontier in modern science, bridging materials chemistry with biotechnology. A deep understanding of the physicochemical processes at this interface is essential for both assessing the environmental impact of nanomaterials and for designing new bioinspired technologies. While much of this field has focused on bacteria and eukaryotes, the domain of Archaea, pivotal to global biogeochemical cycles and a promising resource for bioenergy, remains a comparatively underexplored territory. The unique cellular architecture of archaea, particularly their distinct membrane lipids and crystalline surface layers (S-layers), presents a unique set of rules for nano-bio interactions, making the study of the nano-archaea interfaces a grand challenge of fundamental importance. In this Account, we summarize the biophysical tools and bioengineering strategies developed in our laboratory to probe and program the nano-archaea interaction. We first developed a single-cell anaerobic atomic force microscopy (AFM) technique to overcome the primary technical barrier of measuring these sensitive, strictly anaerobic organisms in situ, which provided an unprecedented window into the archaeal nanomechanical world. This platform enabled us to reveal the critical role of the archaeal S-layer in maintaining the cellular stability and mediating hydrophobic interactions. We then deciphered the complex chemical dialogue between nanoparticles and archaea, discovering the dominant influence of nanoparticle surface chemistry on the nature of the interaction and the ultimate biological response. Building upon this foundation of fundamental understanding, we have rationally designed and constructed several functional nano-archaeal biohybrid systems. These breakthroughs, progressing from tool development to fundamental discovery and finally to functional engineering, not only help fill a theoretical gap in nanointerface science but also provide new strategies and insights for developing next-generation biotechnologies.