Structural Modulation in Short Peptide Crystals from Centrosymmetric to Noncentrosymmetric Achieving Piezoelectricity

Peptide assemblies with noncentrosymmetric supramolecular structures exhibit intrinsic piezoelectricity as highly engineerable piezoelectric biomaterials. In contrast, centrosymmetric packing forming peptide assemblies are typically considered nonpiezoelectric, significantly limiting their functional applicability. Molecular engineering of peptides to modulate the architectural symmetry of assemblies from centrosymmetric to noncentrosymmetric could achieve piezoelectric functionality, which remains largely unexplored. Herein, based on the nonpiezoelectric centrosymmetric structure of glycylglycine (GG) dipeptide assemblies, we designed two chiral tripeptides by incorporating l-phenylalanine at the N-terminus and C-terminus of the GG building block to engineer the noncentrosymmetric crystal packing for modulating the piezoelectric properties. The X-ray diffraction studies showed that l-phenylalanyl-glycyl-glycine (FGG) and glycyl-glycyl-l-phenylalanine (GGF) assemblies crystallized in the noncentrosymmetric orthorhombic <i>P</i>2₁2₁2₁ space group, forming right- and left-handed helical-like structures, respectively. Density functional theory (DFT) calculations revealed that FGG and GGF assemblies exhibited distinct piezoelectric responses, with maximal piezoelectric coefficients <i>d</i>₂₅ of 12.7 and 3.0 pm/V, respectively. FGG crystal-based piezoelectric nanogenerator (PENG) produced stable open-circuit voltage outputs of 1.75 V under an applied force of 53 N, exhibiting robustness and durability over 3000 pressing-releasing cycles. This work explores an effective strategy to modulate the piezoelectric properties of short peptide assemblies from centrosymmetric to noncentrosymmetric structures, establishing new design frameworks and guidelines for engineering high-performance peptide-based piezoelectric biomaterials.