DOI: 10.1021/accountsmr.6c00084 ISSN: 2643-6728

Silica-Based Encoding of Biological Structure, Information, and Activity

Ting Ruan, Muyuyang Lin, Jiangfan Cao, Qi Lei, C. Jeffrey Brinker, Wei Zhu

Conspectus

Preserving the structure, molecular information, and functional activity of biological systems across time remains a central challenge in modern biotechnology. Existing preservation strategies often involve trade-offs: approaches that maintain structural fidelity frequently compromise molecular integrity, whereas methods designed to stabilize biomolecules typically disrupt native architecture or function. Nature, however, provides compelling precedents for long-term biological preservation. Fossils recovered from Siberian permafrost have retained readable genetic material for millions of years, and silicified organisms frequently preserve detailed morphological features together with molecular chemical signatures embedded within mineral matrices. These natural examples suggest that silicification can simultaneously immobilize biological structures and stabilize core biomolecular information. However, fossilization is inherently slow, uncontrolled, and irreversible, unfolding over geological time scales. A key challenge therefore emerges: whether artificial, biomimetic silica shells can be engineered to capture and preserve biological systems with comparable fidelity but under controllable laboratory conditions and across practical time scales. In this context, silica-based encoding is used here to denote more than passive preservation: it converts biological structures, molecular information, and functional states into mineral-stabilized forms that remain readable and, in selected cases, recoverable.

In this Account, we summarize recent advances in a controllable biomimetic silicification platform developed by our group that enables multilevel preservation of biological systems. At the structural level, silica replication produces high-fidelity three-dimensional preservation of biological architectures spanning subcellular organelles, individual cells, and complex tissues, overcoming the conventional compromise between morphological resolution and preservation stability. At the molecular level, in situ encapsulation within a silica matrix substantially enhances the chemical stability of biomacromolecules, allowing genomes, transcriptomes, and proteomes to be preserved at room temperature for extended periods without reliance on cryogenic storage. At the functional level, the approach extends beyond static preservation: enzymatic activity and cellular viability can be retained during encapsulation and subsequently restored after controlled silica removal, enabling the recovery of biological function from preserved samples. These capabilities arise from key physicochemical properties of silica matrices. Their high surface area and tunable chemical environment stabilize biomolecules through non-covalent interactions such as electrostatic attraction and hydrogen bonding, while the mild and controllable dissolution of silica enables on-demand decapsulation with minimal perturbation to molecular integrity and biological activity.

Looking ahead, advancing this technology demands several key research directions. A deeper mechanistic understanding of silica precursor–macromolecule interactions will enable precise control over silicification pathways, facilitating their extension to complex biological systems and integrated multiomics preservation. Concurrently, developing standardized protocols compatible with clinical workflows and biobanks is critical for practical translation. These capabilities could drive novel strategies for long-term biospecimen storage, disease modeling, drug discovery, biosensing, and early biological system reconstruction. Ultimately, by enabling the controllable silica-based encapsulation of biological data, biomimetic silicification provides a powerful framework for preserving and reactivating life, potentially transforming how biological materials are archived, studied, and utilized across the life sciences.

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