Piezoelectric Biomaterials: Ultrashort Helical Peptide Assemblies for Efficient and Environment Friendly Power Generation

Using a simple, minimalistic building block mimic of collagen, we fabricate a peptide-based piezoelectric generator utilizing a helical arrangement of tripeptide. Our results provide a promising device demonstration by molecular engineering of piezoelectricity in bio-inspired nanotechnology.

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We are using the remarkable phenomenon of piezoelectricity quite a few times in everyday life. For example, if we have a quartz watch, it operation is based on the piezoelectricity of quartz crystals. Similarly, piezoelectric igniters are commonly used for butane lighters, gas grills, gas stoves, blowtorches etc. Piezoelectricity is also utilized for the construction of sensors and other devices. Basically, converting mechanical energy into electrical energy is termed as piezoelectricity. This is a quality of materials with noninverse symmetric structure that leads to the conversion of physical deformation into electric output and vise-versa.1,2 Applying mechanical energy to piezoelectric material deforms the crystal structure and induces the movement of the dipole moment within the material, and results an electrical field to develop across the material boundary. In energy research, exploring the possibilities of renewable, sustainable, green energy sources is one of the most significant and challenging issues. The mechanical energy is present throughout the environment in many forms including wind, water flow, mechanical vibration, and human movement. This makes piezoelectricity a promising alternative for energy-related application in a variety of industry purposes. The ability to harvest this energy using nanogenerators is enabling the development of self-powered systems such as sensors for structural health monitoring, environmental measurement, and chemical and biosensing.

Piezoelectricity has long been posited in many natural systems, such as bone, tendon, skin, hair, wood, virus, protein, amino acid, deoxyribonucleic acid (DNA), nucleotides.3 Although, there is significant lack of fundamental understanding of the role of piezoelectric effect in nature, these are believed to be closely related to the health condition. As for example, the mechanical stress on the bone produces electrical signals that are known to promote bone growth, healing, and remodeling. Therefore, piezoelectric materials based on biomimetic are considered as notable candidates for biomedical applications. The nontoxic, noninjurious, and nonimmunogenic nature of these materials would allow building biodevices that can be safely integrated with biological systems for applications such as sensing biological forces, stimulating tissue growth and healing, as well as diagnosing medical problems. However, current piezoelectric devices are predominantly made from a variety of inorganic materials and organic polymers such as zinc oxide (ZnO), poly(vinylidene fluoride-trifluoroethylene) (P(VDF-TrFE)) and single layer molybdenum disulfide (MoS2), which limits their deployment in health monitoring and regenerative medicine due to reliance on toxic starting metals or nonbiodegradable components, complicated synthesis procedures, weak oxidation stability and poor sustainability. Therefore, there is highly active search for natural biocompatible piezoelectric materials.

Intrinsically biocompatible peptide-based structures (e.g., nanostructures) are considered of particular potential as this novel type of ideal components. The directional hydrogen-bonding and aromatic interaction networks are commonly found in peptide structures may mediate the formation of specific dipole alignments, which can produce spontaneous polarization underlying their intrinsic piezoelectric properties. However, the structural instability, weak mechanical strength, and inefficient electrical properties severely impede their extensive application. The use of peptide-based structures as functional piezoelectric materials is an unmet challenge for power harvesting or at bio-machine interfaces.

Our group led by Prof. Gazit is actively exploring the use of the shortest available peptide building blocks that can formed ordered nanostructures of unique physical properties including mechanical, optical, magnetic and electronic.4,5 Now, we design an ultrashort tripeptide, Pro-Phe-Phe, the shortest peptide sequence built only from natural amino acids that organizes into a cross-helical structural arrangement stabilized by intermolecular hydrogen bonds and dry hydrophobic interfaces of Phe residues.6 Measurement of Young’s modulus of the Pro-Phe-Phe assemblies is found to be about 44 GPa, indicating a remarkable stiffness. Reengineering of Pro-Phe-Phe by substituting proline with hydroxyproline (Hyp), an essential component of collagen, affords super-helical assembly with increased number H-bonding and thereby achieves a mechanical rigidity (102 GPa) comparable to that of natural collagen matrices.

Having verified helical conformation, and high mechanical robustness similar to collagen, we use the DFT in collaboration with Prof. Tofail and Prof. Thompson group to predict the piezoelectric constants of the tripeptides. For Pro-Phe-Phe, we observe moderate dij values of up to 3.1 pm V−1 (Fig. 1). However, for Hyp-Phe-Phe, increases the number of non-zero piezoelectric constants in each tensor with the magnitude of the predicted piezoelectric strain constants, dmax = d35 = −27.3 pm V− 1 and d33 = 4.8 pm V− 1. The predicted voltage constants, in the order of 1 V m/N (Hyp-Phe-Phe, gmax = g16 = 1043 mV m/N) is quite high as compare to KNN- based ceramics (g33 = 40 mV m/N), BiB3O6 (g33 = 540 mV m/N). 

Figure 1. Comparison of piezoelectric strain response of different biological and non-biological materials with Pro-Phe-Phe and Hyp-Phe-Phe.

To experimentally validate our predictive modelling, we first employed piezoelectric force microscopy (PFM). The results reveal the vertical coefficient d33eff of Pro-Phe-Phe assemblies to be 2.15 ± 0.86 pm V− 1, which rises to 4.03 ± 1.96 pm V− 1 for Hyp-Phe-Phe. Measuring the shear piezoelectricity of Hyp-Phe-Phe yielded an effective shear piezoelectric coefficient d34eff of 16.12 ± 2.3 pm V− 1, which is higher than the experimentally measured magnitude of LiNbO3 (13 pm V− 1), ZnO (12 pm V− 1), amino acid γ-glycine (10 pm V− 1) and protein/peptide biomaterials M13 bacteriophage (6 –8 pm V− 1) and collagen film (1 pm V− 1).

Finally, to test the potential of our peptide assemblies for energy harvesting and piezoelectric sensing in integrated microdevices, we collaborate with Prof. Yang to design a coin-size power generator (Fig. 2). For Pro-Phe-Phe, under an applied force F = 55 N, the output open-circuit voltage (Voc) reaches to 1.4 V. The corresponding short-circuit current ( Isc) 52 nA, which is significantly higher than the output current obtained from nanogenerators based on M13 bacteriophage virus (6 nA) or fish skin collagen (1.5 –20 nA). Using Hyp-Phe-Phe assemblies as the active layer, similar short-circuit current output is achieved when the applied force is only 23 N, half that applied for Pro-Phe-Phe. High mechanical rigidity of peptide assemblies helps the power generation to be sustained under a cyclic force and the output voltage shows no degradation over 1000 press/release cycles for more than 60 min, indicating the high durability of the peptide-based devices.

Figure 2. Helical peptide-based nanogenerator. a, Photograph and schematic configuration of coin-sized piezoelectric energy generation. b, The measured short circuit current output of Hyp-Phe-Phe under different applied force. c, Comparison of output current of β-sheet forming peptide Phe-Phe with helical peptide Hyp-Phe-Phe.

To understand the relation between atomic level structural organization and macro-scale piezoelectricity, we fabricate a control device using the well-established β-sheet forming dipeptide, Phe-Phe.  Under the same applied force, F = 23 N, the maximum output open-circuit voltage and short-circuit current was only 0.14 V and 3.9 nA clearly demonstrates how differences in the structural organization at the atomic level can bear a dramatic effect on biomaterial piezoelectricity.

Currently, the piezoelectricity of biomaterials is not fully understood at the molecular level. Our demonstration of collagen-level piezoelectricity in rationally designed ultrashort peptides reinforce the value of prediction-led molecular engineering of piezoelectricity to accelerate the deployment of peptides in nanotechnology applications.

Click here for more details about our work in Nature Communications.

References:

  1. Guerin, S. et al. Control of piezoelectricity in amino acids by supramolecular packing. Nat. Mater. 17, 180-186 (2018).
  2. Nguyen, V., Zhu, R., Jenkins, K. & Yang, R. S. Self-assembly of diphenylalanine peptide with controlled polarization for power generation, Nat. Commun. 7, 13566 (2016).
  3. Guerin, S., Tofail, A. M.S. & Thompson, D. Deconstructing collagen piezoelectricity using alanine-hydroxyproline-glycine building blocks. Nanoscale, 10, 9653-9663 (2018).
  4. Kholkin, A., Amdursky, N., Bdikin, I., Gazit, E. & Rosenman, G. Strong piezoelectricity in bioinspired peptide nanotubes. ACS Nano 4, 610-614 (2010).
  5. Tao, Kai, et al. Bioinspired stable and photoluminescent assemblies for power generation. Adv. Mater. 31, 1807481 (2019).
  6. Bera, S. et al. Rigid helical-like assemblies from a self-aggregating tripeptide. Nat. Mater. 18, 503–509 (2019).

Santu Bera

Postdoctoral Researcher, Tel Aviv University