In a groundbreaking advancement that could revolutionize sustainable protein recycling, researchers at Harvard’s John A. Paulson School of Engineering and Applied Sciences (SEAS) have uncovered a fundamental chemical mechanism underlying the denaturation of keratin proteins by salt compounds. Keratin, the fibrous and resilient protein found in hair, wool, feathers, skin, and nails, represents a vast and largely untapped source of biopolymer waste generated annually by the textile and meat-processing industries. The new insight elucidates how lithium bromide, a salt long known for its ability to break down keratin, operates not through direct protein interaction but via subtle restructuring of surrounding water molecules. This discovery heralds the promise of gentler, more efficient, and environmentally friendly protein recycling techniques.
Keratin-rich waste, encompassing billions of tons of often discarded materials such as feathers, wool, and human hair, has long presented a challenge to recycling technologies. Efforts to recover and repurpose these proteins for applications ranging from wound healing dressings to advanced eco-textiles have been stymied by the harsh chemical treatments typically required to untangle and solubilize keratin chains. Conventional denaturation approaches rely heavily on corrosive reagents and energy-intensive processing, resulting in significant environmental impact and high operational costs. SEAS researchers have now turned this paradigm on its head by investigating lithium bromide solutions that can disrupt keratin in a reversible, non-destructive manner, laying the groundwork for sustainable protein upcycling industries.
Leading the study, Kit Parker, Tarr Family Professor of Bioengineering and Applied Physics, combined rigorous experimental protocols with state-of-the-art molecular simulations to probe the interaction between lithium bromide and keratin at the molecular level. Contrary to longstanding assumptions expecting direct salt-protein binding as the denaturation mechanism, the team demonstrated that lithium bromide instead subtly modifies the hydrogen bonding network and dynamics of the surrounding aqueous environment. This environmental modulation induces an energetically favorable condition where the keratin protein spontaneously unfolds, circumventing the need for aggressive chemical attack. This entropy-driven unfolding mechanism challenges traditional views and opens new possibilities for controllable, reversible protein processing.
A pivotal tool in this research was molecular dynamics simulation conducted in collaboration with Professor Eugene Shakhnovich’s laboratory, specializing in protein biophysics. These computational models revealed that lithium bromide effectively partitions the water molecules around protein structures into two distinct subpopulations: bulk water molecules exhibiting typical behavior, and those tightly coordinated or “trapped” by lithium and bromide ions. As lithium bromide concentration increases, the volume of conventional water diminishes, altering thermodynamic conditions to destabilize the folded state of keratin. This novel insight—that the aqueous medium, rather than the protein itself, is the primary target of denaturation—offers a nuanced understanding of biomolecular interactions in salt-rich environments.
The reversible nature of this lithium bromide-mediated denaturation was a particularly fortuitous finding. Proteins extracted via this method can be precipitated and recovered by reintroducing water, reestablishing their structural integrity. This attribute enables not only sustainable extraction processes but also the regenerative recycling of the denaturant salts themselves, minimizing waste and enabling closed-loop biochemical manufacturing systems. By allowing rapid gel-to-solid phase transitions of keratin upon rehydration, the technique holds promise for the scalable production of keratin-based biomaterials, accelerating applications in biomedical engineering such as tissue scaffolding and drug delivery.
This research builds upon a well-established interest within Parker’s group in creating keratin biomaterials with shape-memory properties. Previous observations noted that keratin extracted using lithium bromide forms thick, malleable gels that quickly solidify upon exposure to water, a behavior reminiscent of living tissues. However, prior mechanisms to explain this phenomenon were speculative. The current study provides the mechanistic clarity necessary to optimize these keratin-based materials’ manufacture, tailoring their properties for biomedical uses without compromising environmental sustainability.
The implications also extend far beyond biomedical applications. With the global textile industry generating enormous quantities of keratinous waste, this methodology offers a pathway toward transforming such waste into eco-friendly textiles and biodegradable materials that could integrate into circular bioeconomies. Moreover, keratin’s unique physical and chemical properties position it as a promising candidate for replacing traditional petroleum-based plastics, addressing demand for sustainable material alternatives amid mounting concerns over plastic pollution and resource depletion.
By elucidating the nuanced interplay between salt ions, water structure, and protein conformation, the research team has contributed a critical piece to the puzzle of sustainable protein engineering. Their approach circumvents the damaging effects of direct chemical onslaughts that typically fragment proteins indiscriminately, instead employing a subtle shift in environmental entropy to trigger controlled unfolding. This principle could be generalized to other protein systems, as demonstrated by similar unfolding behaviors observed with fibronectin, reinforcing the broad applicability of the mechanism.
Besides the academic novelty, the practical advances embedded in this work have attracted considerable federal support, reflective of its strategic importance. Funding agencies including the National Institutes of Health and the National Science Foundation, alongside international collaborations such as the Innovation and Technology Commission of Hong Kong SAR, have recognized the potential for this green chemistry approach to reboot protein waste valorization industries. The new approach aligns with global trends prioritizing sustainability, resource efficiency, and circularity in manufacturing, resonating with corporate and governmental stakeholders seeking to reduce environmental footprints.
Viewed through the lens of molecular biophysics, the lithium bromide system offers a model for how seemingly inert solutes profoundly influence biochemical landscapes via water mediation. Such insights challenge reductionist interpretations that often emphasize direct ligand-protein interactions. Instead, the surrounding solvent milieu emerges as a dynamic participant shaping biomolecular behavior—a revelation with implications for drug design, enzyme catalysis, and understanding disease-related protein misfolding.
This transformative research, recently published in the prestigious journal Nature Communications, simultaneously honors the complexity of biological macromolecules and extends practical engineering capabilities for addressing one of the pressing sustainability challenges of our age. By harnessing entropy and water structuring, SEAS scientists have set the stage for a new era of gentle, efficient, and regenerative protein recycling, one that promises to convert biological waste streams into valuable, high-performance biomaterials.
Subject of Research: Lab-produced tissue samples
Article Title: Entropy-driven denaturation enables sustainable protein regeneration through rapid gel-solid transition
News Publication Date: 26-Jul-2025
Web References:
- Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS)
- Kit Parker
- Eugene Shakhnovich
- Nature Communications Article
- Behind the Paper Blog Post
References:
- DOI: 10.1038/s41467-025-61959-9
Image Credits: Michael Rosnach
Keywords
Protein engineering, Engineering, Bioengineering, Biochemical engineering, Biomedical engineering, Biotechnology, Chemical engineering, Separation methods, Materials engineering, Biomaterials, Materials processing, Environmental engineering, Industrial science, Chemistry, Chemical mixtures, Organic chemistry, Organic reactions, Organic compounds, Water chemistry, Water molecules
