Protein-based materials enter a new era with molecular design and AI-driven innovation

The review details how fibrous proteins such as collagen, keratin, and silk, along with adhesive proteins and elastin, can be tailored through chemical modifications and de novo molecular design to achieve precise functionalities.

Proteins are nature’s fundamental building blocks, forming complex machines and dynamic materials that support movement, metabolism, and cellular structure. Their intrinsic biocompatibility and bioactivity have long made them promising candidates for applications in tissue engineering, drug delivery, biosensing, and packaging. However, challenges such as instability under physiological conditions, immunogenicity, and structural variability have limited their widespread use. By integrating modern protein engineering techniques with computational modeling, scientists are now able to manipulate amino acid sequences, folding patterns, and binding sites at the molecular level. These innovations, supported by AI-based structural prediction, offer new solutions to address the long-standing limitations of protein-based materials.

A study (DOI:10.1016/j.bidere.2025.100004) published in BioDesign Research on 26 February 2025 by Shangxian Xie’s & Yaxian Zhou’s team, Huazhong University of Science and Technology & Guangxi Shenguan Collagen Biological Group, overviews fibrous, adhesive, and elastic protein materials, their real-world applications, and strategies for structural optimization to enhance functionality and stability.

This review begins with the classification and properties of natural protein materials, proceeds through their applications in food, biomedical, and environmental sectors, and concludes with strategies for molecular design and optimization. Fibrous proteins like collagen, silk, and keratin provide mechanical support and have been engineered for use in wound healing, bone regeneration, and high-performance fibers. Adhesive proteins from mussels and sandcastle worms inspire underwater adhesives, while elastin and elastin-like polypeptides serve in biomedical scaffolds due to their “stretch-relax” elasticity. In food science, proteins function as additives, stabilizers, and eco-friendly packaging materials, while protein–nanomaterial hybrids enable highly sensitive biosensors for environmental monitoring. Biomedical applications span scaffolds for tissue engineering, drug carriers for targeted therapies, biosensors for health diagnostics, and imaging probes for disease detection. Across all these fields, limitations such as solubility, structural degradation, and limited bioavailability drive the need for targeted structural optimization. To address these challenges, the review explores chemical modifications such as conjugation, amino acid modifications, cross-linking, and grafting. Conjugation strategies enable proteins to be linked with drugs, polymers, or fluorescent dyes to extend functionality, while pegylation improves stability and circulation in drug delivery. Amino acid modifications—including phosphorylation, methylation, and glycosylation—allow fine-tuning of protein activity and interactions, offering therapeutic potential for diseases ranging from cancer to neurological disorders. Cross-linking and grafting further enhance stability and biocompatibility, making protein scaffolds more suitable for implants and biomedical devices. Beyond chemical modification, de novo molecular design supported by computational simulations (such as AlphaFold2, Rosetta, and molecular dynamics platforms like GROMACS) allows researchers to predict and optimize protein structures with unprecedented accuracy. Strategies like binding site redesign, side-chain optimization, and hydrophobic core stabilization are enabling breakthroughs in protein engineering. Importantly, deep learning–based tools now offer capabilities to design proteins with new functions, moving beyond natural templates. These approaches not only enhance performance in current applications but also expand protein functionality to entirely new domains, such as programmable drug release or adaptive biomaterials that respond to environmental cues.

In conclusion, by combining molecular design with computational predictions and experimental validation, researchers can overcome current bottlenecks and accelerate the development of sustainable, biocompatible, and multifunctional biomaterials. By bridging natural diversity with engineered precision, these strategies hold the potential to unlock smarter biomaterials for applications ranging from regenerative medicine and environmental remediation to food innovation and beyond.

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References

DOI

10.1016/j.bidere.2025.100004

Original Source URL

https://doi.org/10.1016/j.bidere.2025.100004

Funding information

This work was supported by the HUST-Shenguan Joint Research Center of Synthetic Biology.

About BioDesign Research

BioDesign Research is dedicated to information exchange in the interdisciplinary field of biosystems design. Its unique mission is to pave the way towards the predictable de novo design and assessment of engineered or reengineered living organisms using rational or automated methods to address global challenges in health, agriculture, and the environment.