S-layer (Glyco)protein lattices: Biophysical principles of antifouling at prokaryotic interfaces.

Surface layer (S-layer) lattices, composed of proteins and glycoproteins, constitute one of the most abundant and conserved supramolecular structures in the prokaryotic world. These self-assembling, two-dimensional arrays represent a major evolutionary investment, often accounting for up to 10% of total cellular protein synthesis. Despite enormous sequence diversity and adaptation to widely different ecological niches, S-layers persist across phylogeny, suggesting a fundamental selective advantage. In this review, we synthesize historical ultrastructural observations with modern atomic-resolution structural data and biophysical principles to demonstrate that antifouling is a general and fundamental function of all bacterial and archaeal S-layers. We argue that antifouling arises from a sophisticated synergy of lattice dynamics, crystalline nanotopography, electrostatic mosaicity, fragmented hydrophobicity, structured hydration shells and frequently glycan-mediated steric repulsion. We specifically place S-layer antifouling into the physical framework of life at low Reynolds numbers, where even minimal surface fouling imposes severe energetic penalties on nutrient acquisition and motility. We also highlight the S-layer as a tunable interface that suppresses non-specific fouling while precisely gating specific molecular interactions and community formation. Finally, we discuss how this universal biophysical strategy provides a powerful blueprint for biomimetic surface engineering in (nano)biotechnology, synthetic biology, and materials science.