Tissue-derived cultured cells exhibit a remarkable range of morphological features in vitro, depending on phenotypic expression and environmental interactions. Translation of these cellular architectures into inorganic materials would provide routes to generate hierarchical nanomaterials with stabilized structures and functions. Here, we describe the fabrication of cell/silica composites (CSCs) and their conversion to silica replicas using mammalian cells as scaffolds to direct complex structure formation. Under mildly acidic solution conditions, silica deposition is restricted to the molecularly crowded cellular template. Inter-and intracellular heterogeneity from the nano-to macroscale is captured and dimensionally preserved in CSCs following drying and subjection to extreme temperatures allowing, for instance, size and shape preserving pyrolysis of cellular architectures to form conductive carbon replicas. The structural and behavioral malleability of the starting material (cultured cells) provides opportunities to develop robust and economical biocomposites with programmed structures and functions.sol-gel | biomineralization | biopreservation | frustule T he synthesis of inorganic materials with controlled and complex forms has been facilitated through discoveries such as vesicle, micelle, and liquid crystalline templating of silicates (1-3), which provided inspiration to explore a range of templating strategies based on self-assembled molecular precursors (4-8), colloids (9-11), and biological templates and vessels (12)(13)(14). A driving force for these efforts is the many complex inorganic structures found in nature. An oft-cited example is the hierarchical composites built by silica condensing microorganisms such as diatoms, which have generated substantial scientific interest for over a century (15). Diatoms display complex three-dimensional (3D) architectures with great structural control over nano-to millimeter length scales. However, despite some success toward elucidating mechanisms of diatom biomineralization, the in vitro synthesis of 3D diatom-like forms has remained elusive. Diatom silica has found numerous applications including as a chemical stabilizer, absorbent, filter medium, and fine abrasive, and the lack of synthetic analogues has facilitated recent investigations to employ diatom frustules as starting materials for shape-preserving chemical transformations into functional nanomaterials (16)(17)(18). Given the potential of this biosilica, it would be desirable to be able to wield control over the silica structure to achieve broader applicability (19); however, strategies to direct diatom morphology using chemical (20) and genetic approaches (21) has proven challenging. Therefore, an ability to generate cell frustules from more malleable templates such as mammalian cells would provide greater access to natural and engineered cell heterogeneity-both structure and function-to be exploited in the design of complex materials.To these ends, biomineralization by silica condensing microorganisms...