Self-Assembly of Bioactive Peptides: An Innovative Pathway and Core Value in Functional Food Development

The self-assembly of bioactive peptides has become a research hotspot and a central direction in food science. Its core value lies in the spontaneous formation of ordered nanostructures—such as nanofibers, micelles, and hydrogels—which precisely addresses the industry's key challenges of gastrointestinal degradation and low bioavailability of functional compounds. This opens a new path for the development of precision nutrition foods and the innovative design of functional carriers. However, challenges such as unclear in vivo behavior and unverified safety remain.The following sections will elaborate on the practical value and application potential of peptide self-assembly in the food sector, focusing on its underlying principles, core advantages, application scenarios, and developmental challenges.

1. The Core Logic of Self-Assembly: From Molecules to Structure Formation

Bioactive peptide self-assembly is a spontaneous and controllable process, primarily driven by the synergistic action of non-covalent forces such as hydrogen bonding, hydrophobic interactions, electrostatic interactions, and π-π stacking, ultimately forming multidimensional structures like nanofibers, micelles, and hydrogels. This process is regulated by two sets of factors: (1) Intrinsically, peptides rich in aromatic amino acids (phenylalanine, tyrosine), proline, or alternating hydrophobic-hydrophilic sequences possess a stronger propensity for self-assembly. (2) Extrinsically, environmental factors like pH, temperature, peptide concentration, and ionic strength can precisely modulate the assembly morphology. For example, pH changes can trigger alterations in the ionization state of peptide chains, enabling reversible switching between assembly and disassembly, allowing adaptation to the complex gastrointestinal environment.

2. Core Advantages: Dual Enhancement of Digestive Adaptability and Bioactivity

      Enhanced Digestive Stability

The spatial structures formed via self-assembly create a physical barrier that hinders digestive enzyme diffusion and shields cleavage sites, significantly reducing the risk of gastrointestinal degradation. For instance, casein peptides co-assembled with ferulic acid retained 79.12% of the original peptides after gastric digestion. Zinc ion-induced self-assembly of oat peptides maintained a 53.2% retention rate post-gastrointestinal digestion, far exceeding that of unassembled peptides. Some assemblies also exhibit pH responsiveness, maintaining integrity in stomach acid and dissociating to release active components upon entering the intestines, achieving targeted delivery.

      Retained and Enhanced Multifunctional Bioactivity

Assembled peptides not only demonstrate structural stability but also retain or even enhance their original biological activities. Regarding antioxidant activity, self-assembled nanoparticles from ovalbumin peptides achieved a DPPH radical scavenging rate of 37.44%, effectively protecting cells from oxidative damage. In terms of antimicrobial activity, self-assembly can increase the charge density of antimicrobial peptides, enhancing their inhibitory effects against both Gram-positive and Gram-negative bacteria. Additionally, they possess potential functions like anti-inflammation and neuroregulation, and can act as carriers to cross biological barriers (e.g., the blood-brain barrier).

3. Core Application Scenarios in the Food Sector

      Efficient Delivery of Functional Components

As carriers, self-assembling peptides can efficiently encapsulate hydrophobic bioactive compounds like curcumin, lutein, and vitamin D3, achieving encapsulation efficiencies as high as 97.38%. They facilitate transport across the intestinal epithelial barrier via transcellular or paracellular pathways, significantly improving bioavailability. For example, sesame peptide-based self-assembled carriers increased the bioavailability of β-carotene by 2.73 times, and zein peptide nanoparticles achieved over 85% encapsulation efficiency for lutein.

      Food Flavor and Quality Optimization

Self-assembly can reduce the exposure of hydrophobic amino acids in peptides, masking bitter tastes. It can also encapsulate compounds with undesirable flavors, such as capsaicin or quercetin, reducing their contact with sensory neurons and improving food palatability. Furthermore, self-assembling peptides can serve as food-grade emulsifiers to stabilize emulsions containing hydrophobic actives, or be used in food packaging, leveraging their antimicrobial and antioxidant properties to extend the shelf life of fresh foods.

4. Key Optimization Pathways for Enhancing Efficacy

To further strengthen the application value of self-assembling peptides, current research focuses on two core optimization directions: (1) Precise peptide sequence design, by incorporating D-amino acids, charged residues, or utilizing AI tools (e.g., AGGRESCAN, molecular dynamics simulations) for high-throughput screening of peptides with high digestibility resistance, shortening R&D cycles. (2) Introducing polysaccharides​ (e.g., konjac glucomannan, sodium alginate) to form hybrid hydrogels, enhancing structural rigidity to improve digestive stability while optimizing carrier-actives interactions.

5. Non-negligible Safety Concerns and Industry Challenges

Despite the promising prospects, self-assembling peptides face multiple practical hurdles. Regarding safety, nanostructures may penetrate cellular barriers and potentially trigger inflammatory responses. The long-term toxicity of residual organic solvents, metal ions from preparation processes, or chemically modified peptides is not fully understood. Technically, the self-assembly behavior of peptides under in vivo physiological conditions remains unclear. The gap between in vitro simulations and actual in vivo absorption, as well as the interaction mechanisms between carriers and active components, requires further in-depth study.

6. Future Outlook

Future research should focus on three main directions: (1) Elucidating the principles of in vivo self-assembly and establishing evaluation models closer to the human body. (2) Developing low-cost, scalable preparation processes to drive technology industrialization. (3) Strengthening safety-by-design principles and systematically evaluating the long-term consumption safety of modified peptides and residual ions. With the integration of fundamental research and applied technology, self-assembling peptides are expected to become core carriers for functional foods and precision nutrition formulations, propelling the food industry towards a transformation characterized by "high efficiency, precision, and safety."

Original Article：

Pan R, Li K, Xu J, et al. Self-Assembly of Bioactive Peptides: A Novel Perspective for Digestive Adaptation and Functional Food Design[J]. Trends in Food Science & Technology, 2026: 105533.