Gelatin is the thermally and hydrolytically denatured product of collagen, the most abundant protein in animals, and, further, it has been utilized extensively for industrial, pharmaceutical, and medical applications. [1,2] At elevated temperature, gelatin exists predominantly in the form of flexible, unfolded coils in solution and can be partially renatured to the ordered, collagen-like helixes upon cooling to room temperature.[1±3] Intensive research has been done on the intricate folding of collagen from random coils to its conformation in the biologically active form. Yet, surprisingly little attention has been paid to the unfolded state, although the insight is emerging that the prevailing dogma may be wrong in depriving unfolded proteins of any biological importance. [4,5] Herein, the electrostatic-force-driven self-assembling behavior of acid-processed gelatin polypeptides has been investigated through the predominantly seeded aggregation growth of denatured gelatin chains, which are selectively adsorbed on citrate-stabilized gold nanoparticles. After mechanical stabilization with a thin layer of silica, the resulting nanometer-sized gold-loaded silica nanocapsules can be directly used for studying the structure and morphology of self-assembled nanoaggregates of gelatin using functional gold nanoparticles as optical and electronic probes. The bifunctional gelatin±silica nanocapsules filled with gold nanoparticles may be further functionalized with biomolecules using well-established silica surface chemistry and, in addition, substances can be encapsulated in the swollen gelatin nano-aggregates for potential bioimaging, diagnostics, drug delivery, etc. This synthetic approach has also been extended to various silica-coated biomolecules, such as polysaccharides and, in addition, it provides insight for creating novel smart bionanostructures. As observed in Figure 1A, well-dispersed gelatin-stabilized gold nanoparticles were prepared using a synthetic procedure described in the Experimental section. Interestingly, the additional silica coating of gelatin-stabilized gold nanoparticles can create novel nanometer-sized gold-loaded silica nanocapsules instead of silica-coated gold nanoparticles, as shown in Figure 1B. All the resulting silica nanocapsules have a uniform silica shell~10 nm in thickness, and the resulting large cavity~40 nm in diameter is filled with swollen gelatin in water, as indicated by the random distribution of the gold nanoparticles (different locations and positions) in the interior of the nanocapsules and by their distinct absorption properties. The cavity volume of a nanocapsule is ca. 18 times larger than the volume of a gold nanoparticle. When citrate-stabi- . Transmission electron microscopy (TEM) images of A) gelatinstabilized gold nanoparticles, and B) silica-coated, gelatin-stabilized gold nanoparticles (nanometer-sized gold-loaded gelatin/silica nanocapsules); C) UV-vis absorption spectra of a) citrate-stabilized gold nanoparticles, b) gelatin-stabilized gold nanoparticles, c) si...