Interaction of Polypeptides with Hair Under Different Reducing Environments

Modern hair care product development increasingly relies on bioactive ingredients, particularly peptides and proteins, aiming to repair hair damaged by chemical treatments (such as bleaching and dyeing) at the molecular level. However, the efficacy of these components is not constant; their interaction with hair is profoundly influenced by the chemical environment within the formulation. An article titled "Interaction of polypeptides with hair in different reducing environments" addresses a core challenge in the hair care industry—repairing hair structure damaged by chemical bleaching/dyeing. It systematically investigates the impact of reducing environments on the interaction and repair efficacy of different polypeptides/recombinant proteins with damaged hair. The study clarifies that the molecular weight, cysteine content, and the accessibility of cysteine within the polypeptide structure are key factors determining repair effectiveness. This provides crucial scientific evidence for the precise formulation design and scenario-specific application of peptide-based active ingredients in hair care.

1. Research Background

The structural integrity and mechanical properties of hair fundamentally depend on the disulfide bonds formed by the abundant cysteine residues in keratin. Oxidative treatments like bleaching irreversibly break disulfide bonds and degrade keratin, leading to raised and detached cuticles, damaged cortex structure, and ultimately manifesting as brittle hair, reduced elasticity, and loss of luster. Peptides and keratin-derived components are currently the core active ingredients in hair repair products. However, the industry lacks a systematic understanding of how reducing environments, commonly used in scenarios like perming or straightening (e.g., with reducing agents like thioglycolic acid), affect the binding and repair performance of such ingredients with hair.

This study aims to address the following three core questions:

• Under three distinct environments—without reducing agents, with thioglycolic acid, and with thioglycolic acid plus thiobenzyl ether—evaluate the repair efficacy of four characteristic polypeptides/proteins on severely bleached and damaged hair.

• Elucidate how the molecular weight, cysteine content, distribution, and accessibility of polypeptides influence their localization within the hair (cuticle vs. cortex) and their interaction modes with keratin.

• Identify the optimal application scenarios (reducing or non-reducing) for polypeptides with different characteristics, providing theoretical guidance for developing efficient, targeted hair care product formulations.

2. Research Methodology

The study established a standardized, controlled system involving a damage model and testing protocol:

• Test Polypeptides:​ Included a synthetic small keratin peptide (KP), recombinant fusion proteins (ELP-KP and BSK), and hydrolyzed keratin extracted from human hair. They differed significantly in molecular weight (1.6 kDa to >40 kDa) and cysteine content (2 to over 20 residues).

• Damage Model and Formulations:​ Asian black hair underwent 7 bleaching cycles to create a severe damage model. Polypeptides were dissolved in three different alkaline (pH 9) ethanol-based formulations: a base formula (F1, no reducing agent), a reducing formula (F2, containing 1% thioglycolic acid), and an enhanced reducing formula (F3, containing F2 components plus 0.5% thiobenzyl ether).

• Efficacy Evaluation System:​ A multi-dimensional assessment was conducted using tensile testing (evaluating Young's modulus, reflecting mechanical strength), wet-state differential scanning calorimetry (analyzing the thermal stability of the keratin α-helix), fluorescence microscopy imaging (observing polypeptide localization and penetration in hair cross-sections), and scanning electron microscopy (observing hair surface morphology).

3. Research Findings

The study revealed clear deterministic relationships between "polypeptide characteristics - reducing environment - repair mechanism - final outcome":

3.1 Repair efficacy is highly dependent on the match between polypeptide characteristics and the reducing environment:

• Small KP peptide:​ Performed best in the mild, non-reducing environment (F1), increasing hair Young's modulus by 39%. Its repair relies on an intact structure for deep penetration into the hair shaft. Adding reducing agents (F2/F3) disrupted its redox state, leading to reduced efficacy.

• High molecular weight, high cysteine proteins (BSK and hydrolyzed keratin):​ Showed significant repair in the reducing environment (F2). BSK increased Young's modulus by 25% in F2, and hydrolyzed keratin by 33%. The reducing agent breaks hair keratin's disulfide bonds, exposing numerous free thiol groups, which form new disulfide crosslinks with these proteins, thereby restoring strength.

• ELP-KP fusion protein:​ Ineffective in all environments. This is because its cysteine residues are buried by the elastin-like sequence, preventing effective binding to hair keratin, and it lacks a local amino acid environment conducive to disulfide bond formation.

3.2 Polypeptide molecular weight directly determines its localization within hair and repair mode:

• KP (small molecule):​ In the absence of reducing agents, it efficiently penetrates the cuticle, distributes uniformly in the cortex, achieving "deep repair" from the inside.

• BSK and hydrolyzed keratin (large molecules):​ Primarily accumulate in the cuticle layer, repairing by filling gaps and forming a protective film on the hair surface, representing "surface repair." Only small fragments within hydrolyzed keratin could minimally enter the cortex.

• ELP-KP:​ Exhibited extremely weak fluorescence signals, confirming its near-total failure to bind effectively to hair.

3.3 Polypeptides can enhance the thermal stability of hair keratin, but the reducing environment interferes with detection:

• The denaturation peak of the keratin α-helix was clearly detected only in non-reducing samples. The reducing environment may disrupt the matrix structure of the cortex, making the denaturation peak undetectable.

• In the detectable F1 group: BSK treatment caused the most significant increase in denaturation temperature, indicating it enhanced structural thermal stability via surface crosslinking. KP treatment resulted in the largest increase in denaturation enthalpy, proving that by deeply penetrating and repairing internally, it significantly enhanced the ability of the keratin secondary structure itself to resist thermal damage.

3.4 The synergistic effect of thiobenzyl ether is limited:

• Comparing F2 and F3 formulations, adding thiobenzyl ether only slightly improved the repair efficacy of hydrolyzed keratin, with no significant positive effect on BSK or KP. This indicates that thioglycolic acid is the core component enabling polypeptide-hair crosslinking under reducing conditions in this system.

4. Conclusion and Application

In summary, the interaction between polypeptides and hair, and the resulting repair efficacy, are not solely determined by the reducing environment. The molecular weight, cysteine content, and site accessibility of the polypeptides are more fundamental determining factors. Small peptides with exposed cysteine sites are suitable for mild, deep-repair scenarios without reducing agents. High molecular weight proteins with high cysteine content are more suitable for perming/straightening scenarios containing reducing agents, achieving effective repair through cuticle film formation and crosslinking.

This study clarifies the optimal application scenarios for different polypeptide-based hair repair ingredients, providing precise formulation design guidance for cosmetic companies developing such products. Furthermore, it validates that these bio-based polypeptides can replace traditional, potentially harmful chemical repair agents, establishing an experimental foundation for the development of a new generation of environmentally friendly and mild hair care products.

Original Article：

Carvalho J P, Costa A F, Gonçalves F, et al. Interaction of polypeptides with hair in different reducing environments[J]. International Journal of Biological Macromolecules, 2026: 150107.