Realization of a self-assembled, nontoxic and eco-friendly piezoelectric device with high-performance, sensitivity and reliability is highly desirable to complement conventional inorganic and polymer based materials. Hierarchically organized natural materials such as collagen have long been posited to exhibit electromechanical properties that could potentially be amplified via molecular engineering to produce technologically relevant piezoelectricity. Here, by using a simple, minimalistic, building block of collagen, we fabricate a peptide-based piezoelectric generator utilising a radically different helical arrangement of Phe-Phe-derived peptide, Pro-Phe-Phe and Hyp-Phe-Phe, based only on proteinogenic amino acids. The simple addition of a hydroxyl group increases the expected piezoelectric response by an order of magnitude (d₃₅ = 27 pm V⁻¹). The value is highest predicted to date in short natural peptides. We demonstrate tripeptide-based power generator that produces stable max current >50 nA and potential >1.2 V. Our results provide a promising device demonstration of computationally-guided molecular engineering of piezoelectricity in peptide nanotechnology.

Most natural biomolecules may exist in either of two enantiomeric forms. Though in nature, amino-acid biopolymers are characterized by L-type homochirality, incorporation of D-amino acids in the design of self-assembling peptide motifs has been shown to significantly alter enzyme stability, conformation, self-assembly behavior, cytotoxicity and even therapeutic activity. However, while functional metabolite assemblies are ubiquitous throughout nature and play numerous important roles including physiological, structural or catalytic functions, the effect of chirality on the self-assembly nature and function of single amino acids is not yet explored. Herein, we investigated the self-assembly mechanism of amyloid-like structure formation by two aromatic amino acids, phenylalanine (Phe) and tryptophan (Trp), both previously found as extremely important for the nucleation and self-assembly of aggregation-prone peptide regions into functional structures. Employing D-enantiomers, we demonstrate the critical role that amino acid chirality plays in their self-assembly process. The kinetics and morphology of pure enantiomers is completely altered upon their co-assembly, allowing to fabricate different nanostructures that are mechanically more robust. Using diverse experimental techniques, we reveal the different molecular arrangement and self-assembly mechanism of the DL-racemic mixtures that resulted in the formation of advanced supramolecular materials. This study provides a simple yet sophisticated engineering model for the fabrication of attractive materials with bionanotechnological applications.

Stimuli-responsive hydrogels can respond to external stimuli with a change in the network structure and thus have potential application in drug release, intelligent sensing, and scaffold construction. Peptides possess robust supramolecular self-assembly ability, enabling spontaneous formation of nanostructures through supramolecular interactions and subsequently hydrogels. Therefore, peptide-based stimuli-responsive hydrogels have been widely explored as smart soft materials for biomedical applications in the last decade. Herein, we present a review article on design strategies and research progress of peptide hydrogels as stimuli-responsive materials in the field of biomedicine. The latest design and development of peptide hydrogels with responsive behaviors to stimuli are first presented. The following part provides a systematic overview of the functions and applications of stimuli-responsive peptide hydrogels in tissue engineering, drug delivery, wound healing, antimicrobial treatment, 3D cell culture, biosensors, etc. Finally, the remaining challenges and future prospects of stimuli-responsive peptide hydrogels are proposed. It is believed that this review will contribute to the rational design and development of stimuli-responsive peptide hydrogels toward biomedical applications.