Directed deposition of silver on the surface of single, soluble enzyme molecules was made possible by controlled conjugation of new silver-reducing moieties to the surface of the enzyme molecule and their reaction with silver ions. Molecular enzyme-silver hybrids carrying low or high crystalline silver deposited on their surface were obtained, retaining their solubility and enzymatic activity. The feasibility of "wiring" of the active site of glucose oxidase-silver hybrid thus obtained to platinum electrode was readily demonstrated enabling glucose determination in the absence of oxygen.Electroless deposition of metals has many applications in fabrication on the basis of micro-and nanotechnologies, for example, interconnects and packaging affected by Cu, Co, Ni, and Ag high-quality ultrathin films, deposited on solid substrates. 1 In recent years, several attempts were made to adopt electroless deposition technologies practiced in the microelectronics industry for the fabrication of new hybrids made of biological templates, for example, DNA and protein arrays for the synthesis of interconnects. Within this context, metallization by electroless deposition of protein-made natural arrays was recently successfully demonstrated for the fabrication of nanowires from microtubules, 2-6 viral envelopes, 7-9 amyloid fibers, 10 and actin. 11 These metallizations were directed to the substrate's surface by the adsorption of palladium or platinum ions followed by their chemical reduction 2-5,7-9 or by surface labeling with colloidal gold particles. 10,11 Enlargement of the nucleation sites thus obtained into continuously deposited metallic films was carried out by immersion in plating solution containing the metal ions of choice such as Ag +1 or Ni +2 and reducing agents such as NaBH 4 or dimethylaminoborane. This nucleation/growth mechanism led to the formation of relatively thick metal deposits, for example, 10-35 nm. 4 Here, we propose and demonstrate feasibility of a novel mechanism for directing silver metallization to the surface of single, soluble enzyme molecule, enabling the construction of a very thin metallic film on its surface, with retention of its biological activity and solubility. Such soluble hybrids of active enzymes are expected to provide novel molecular tools for applications requiring "wiring" of nanosized sensors to electrodes and composite biochips. 12 The new method is based on coupling of a reducing agent to the surface of soluble enzyme molecules, followed by removal of nonbound reducer. Addition of ion metals will lead to the formation of nucleation sites accompanied by local growth leading to the formation of metallic "patches". The density and continuity of these patches may be controlled by the density of the reducing moieties, displayed on the surface of the enzyme as monolayered or multilayered arrays. This process should result in the formation of metallic coating stretching out close enough to the catalytic site of the enzyme without blocking it to substrate access.The enzyme selected for f...