Biomimetic Materials – From Curiosity Driven Research to Next-Generation of Sustainable and Biomedical Materials
Ali Miserez, School of Materials Science and Engineering, Center for Sustainable Materials (SusMat); School of Biological Sciences, Nanyang Technological University (NTU), Singapore
Host: Cecília Roque, UCIBIO NOVA
ZOOM link: https://ucibio.pt/l/GuestSeminars
Bio-based polymers hold great potential as alternative sources of petro-chemical based polymers. They are eco-friendly, non-toxic, and their degradable products are harmless, such as amino acids in the case of protein materials. However, they still represent a tiny fraction compared to the market of synthetic polymers, despite the fact that biopolymers often exhibit remarkable load-bearing performance that can compete or even exceed the best synthetic polymers. For example, silk has been known for decades to exhibit outstanding mechanical properties that surpass those of many synthetic fibers, and there has been an outburst of activity to produce artificial silk by genetic engineering. Likewise, fully proteinaceous or protein/polysaccharides hard tissues found in Nature – for instance squid beak  and sucker ring teeth (SRT) [2,3] from cephalopods– can exhibit a combination of mechanical properties on par or superior with the best synthetic polymers. If one wants to replicate these load-bearing proteins artificially, it is critical to determine their primary structure. This task has historically been a major bottleneck exacerbated by the lack of genomic data from many model organisms. In this talk, I will describe our pioneer efforts in establishing Next-Generation sequencing (RNA-Seq) in the context of biomimetic materials engineering [4,5], which enables the rapid discovery of novel protein materials.
I will illustrate our efforts in deploying this platform towards the intriguing squid SRT, a type of protein-based materials with excellent mechanical performance. We have shown that SRT are entirely made of modular “suckerin” proteins, which assemble into a supramolecular network reinforced by nano-confined β-sheets . SRTs exhibit thermoplastic properties, which can be exploited to re-process the proteins into complex shapes by simple lithographic techniques  and make SRT a promising material as “bio-ink” for 3D bioprinting  or as eco-friendly adhesives .
Protein polymers also hold attractive potential for biomedical applications. As a representative example, I will describe a new generation of phase-separating peptides derived from the squid beak  that we have engineered to deliver any type of macromolecular therapeutics (mRNA, pDNA, proteins, CRISPR/Cas9, etc…) intracellularly [10,11]. These peptides self-assemble into coacervate microdroplets  by pH-triggered Liquid-Liquid Phase Separation (LLPS), during which the therapeutics are instantaneously recruited within the droplets. The loaded microdroplets cross the cell membrane by a non-classic endocytosis pathway, are cargo-agnostic, non-cytotoxic, and capable to release their cargo in the cytosol while maintaining their bioactivity . Overall, this platform represents a general and robust strategy for the intracellular delivery of a range of macromolecular modalities with promising potential in oncology, gene therapy, or metabolic diseases.
Ali Miserez is a Full Professor of Biomimetic and Bioinspired Materials at Nanyang Technological University (Singapore), which he joined in 2009, with joint appointments in the School of Materials Science and Engineering and the School of Biological Sciences. He obtained his PhD (2003) from EPFL (Switzerland) in the field of composite and mechanics of materials. From 2004 to 2009, he was a post-doctoral fellow at UC Santa Barbara, where he expanded his research towards biomimetic engineering and biochemistry of extra-cellular tissues. Miserez’s research aims at revealing the molecular, physico-chemical, and structural principles from unique biological materials, and at translating their molecular design into novel biomimetic materials, including for healthcare applications. At NTU, he is currently the founding Director of the “Center for Sustainable Materials".
His interdisciplinary research has been published in over 100 articles in a wide range of journals across the Physical and Life Sciences, including in Science, Nature Materials, Nature Biotechnology, Nature Chemical Biology, Nature Chemistry, Biomacromolecules, ACS Nano, Acta Biomaterialia, Advanced Materials, J. Biological Chemistry, Polymer Chemistry, etc. He has delivered numerous invited talks, including at Gordon Research Conferences in the field of bioinspired materials, biointerfaces, biomineralization, and intrinsically disordered proteins.
1. Miserez, A., Schneberk, T., Sun, C., Zok, F. W. & Waite, J. H. The Transition from Stiff to Compliant Materials in Squid Beak. Science 319, 1816-1819, (2008).
2. Hiew, S. H. & Miserez, A. Squid Sucker Ring Teeth: Multiscale Structure–Property Relationships, Sequencing, and Protein Engineering of a Thermoplastic Biopolymer. ACS Biomaterials Science & Engineering 3, 680–693, (2017).
3. Guerette, P. A. et al. Nanoconfined β-sheets Mechanically Reinforce the Supra-Biomolecular Network of Robust Squid Sucker Ring Teeth. ACS Nano 8, 7170–7179, (2014).
4. Guerette, P. A. et al. Accelerating the Design of Biomimetic Materials by Integrating RNA-Seq. with Proteomics and Materials Science. Nature Biotechnology 31, 908–915, (2013).
5. Miserez, A., Yu, J. & Mohammadi, P. Protein-Based Biological Materials: Molecular Design and Artificial Production. Chemical Reviews 123, 2049-2111, (2023).
6. Ding, D. et al. Squid Suckerin Microneedle Arrays for Tunable Drug Release. Journal of Materials Chemistry B 5, 8467–8478, (2017).
7. Latza, V. et al. Multi-Scale Thermal Stability of a Hard Thermoplastic Protein-Based Material. Nature Communications 6: 8313, (2015).
8. Deepankumar, K. et al. Supramolecular β-Sheet Suckerin–Based Underwater Adhesives. Advanced Functional Materials 30, 1907534, (2020).
9. Tan, Y. P. et al. Infiltration of a Chitin Scaffold by Protein Coacervates Defines the Squid Beak Mechanical Gradient. Nature Chemical Biology 11, 488–495, (2015).
10. Sun, Y. et al. Phase-separating peptides for direct cytosolic delivery and redox-activated release of macromolecular therapeutics. Nature Chemistry 14, 274-283, (2022).
11. Sun, Y. et al. Redox-Responsive Phase-Separating Peptide as a Universal Delivery Vehicle for CRISPR/Cas9 Genome Editing Machinery. ACS Nano 17, 16597-16606, (2023).
12. Liu, J., Spruijt, E., Miserez, A. & Langer, R. Peptide-based liquid droplets as emerging delivery vehicles. Nature Reviews Materials, (2023).