Ehud Gazit, Department of Molecular Microbiology and Biotechnology and Department of Materials Science and Engineering, Tel Aviv University

Solid-State Biology: From biological association to novel organic nano-materials of exceptional physical properties

Our lab is extensively involved in the minimalistic, reductionist and non-biased quest towards the most fundamental molecular recognition and self-assembling modules in nature that possesses unique physical properties including mechanical, optical, electronic, and piezoelectric.

For many years, our identification of ß-sheet-like arrangement of ultrashort dipeptides, most notably diphenylalanine (Phe-Phe) and its derivatives, had prompted the basic study and technological application of such short peptides. These peptides offer the combination of the materials properties of natural and synthetic polyamide with the ease and facile synthesis of the dipeptides. These structures show remarkable chemical and physical stability and also extraordinary mechanical properties. Moreover, the formed nanostructures show remarkable optical priorities that could be attributed to the molecular organization of quantum dots with radii of about 1.3 nm, a much smaller value that could be obtained by lithography techniques and that is consistent with the crystalline organization of the building blocks at the nano-scale.

The nanostructures show also unique piezoelectric properties that are also attributed to their crystalline assembly. The assemblies revealed electric polarization directed along the tube axis demonstrating linear deformation without irreversible degradation in a broad range of driving voltages. Comparison with well-known piezoelectric LiNbO 3 and lateral signal calibration yields sufficiently high effective piezoelectric coefficient values of at least 60 pm/V.

We recently extended our studies in different directions. The first is the identification and utilization of minimalistic peptides that form helical structures. We realized that the Pro-Phe-Phe could form helical assemblies with notable physical properties. Inspired by nature, we replaced the proline with hydroxyproline to achieve Young's modulus comparable to titanium.  One key direction is the use of co-assembly instead of self-assembly to achieve novel architectures and desired mechanical and electrical properties.

Finally, in recent years, we become more and more interested in metabolites, both as the basis for the disease but also as building blocks for materials with mechanical, optical, and electronic properties. Many of the properties that are found in short peptides could be observed also in metabolite assemblies. Intriguingly, natural systems also use metabolites to form optically-active assemblies such as tapetum lucidum retro-reflectors. 

Selected References
1. Tao, K., Makam, P., Aizen, R., & Gazit, E. (2017) Self-Assembling Peptide Semiconductors. Science 358, eaam9756.
2. Bera, S., Mondal, S., Xue, B., Shimon, L. J. W., Cao, Y., & Gazit, E. (2019) Rigid Helical-like Assemblies from a Self-Aggregating Tripeptide. Nat. Mater. 18, 503–509.
3. Makam, P., Yamijala, S. S. R. K. C., Tao, K., Shimon, L. J. W., Eisenberg, D. S., Sawaya, M. R., Wong, B. M., & Gazit, E. (2019) Nonproteinaceous Hydrolase Comprised of Phenylalanine Metallosupramolecular Amyloid-Like Structure. Nat. Catal. 2, 977–985. (Featured in a "News and Views" article at: Nature Catal. 2, 949–950).
4. Levin, A., Hakala, T., Schnaider, L., Bernardes, G., Gazit, E. & Knowles, T.P.J. (2020) Biomimetic Peptide Self-Assembly for Functional Materials. Nat. Rev. Chem. 4, 615-634.
5. Bera, S., Guerin, S., Yuan, H., O'Donnell, J., Reynolds, N.P., Maraba, O., Ji, W., Shimon, L.J.W., Cazade, P.A., Tofail, S.A.M., Thompson, D., Yang, R. & Gazit E. (2021).
Molecular Engineering of Piezoelectricity in Collagen-Mimicking Peptide Assemblies. Nat. Commun. 12, 2634.
6.  Chakraborty, P., Bera, S., Mickel, P., Paul, A., Shimon, L. J. W., Arnon, Z. A., Segal, D., Král, P. & Gazit, E. (2022) Inhibitor-Mediated Structural Transition in a Minimal Amyloid Model. Angew. Chem. Int. Ed. Engl. 61, e202113845.