
**Rational design of self-assembling amyloid building blocks as scaffolds for
novel biomaterials**
Prof. Anna Mitraki
Professor, Department of Materials Science and Technology, [University of
Crete](https://scholar.google.com/citations?view_op=view_org&hl=es&org=5577346756842911914),
and IESL/FORTH
Self-assembling peptides gain increasing interest as scaffolds for novel
bionanomaterials; rationally designed self-assembling building blocks are
especially attractive. We have been focusing on modular designs that consist
of a central ultrashort amphiphilic motif derived from the adenovirus fiber
shaft. This central amphiphilic motif can be further modified with amino acids
targeted for various functionalities. We have been using a combination of
computational (in collaboration with Prof. [Phanourios
Tamamis](https://engineering.tamu.edu/chemical/profiles/tamamis-
phanourios.html) at Texas A& M University) and experimental approaches towards
such rational self-assembling peptide designs [1]. The designer peptides self-
assemble into fibrils that are structurally characterized with Transmission
Electron Microscopy, Scanning Electron Microscopy and X-ray fiber diffraction;
these fibrils were previously targeted to bind to metal nanoparticles, silica,
calcium, and more recently, cells [2]. Recently, we demonstrated that self-
assembling peptide sequences derived from HIV gp120 V3 loop sequences and
amyloid beta peptide that comprise a central self-assembling beta sheet core,
with suitable selected replacements at flexible positions can serve as
designable scaffolds for amyloid-based materials [3]. On that basis, we
designed and studied functional amyloid materials with cesium binding,
deposition and capture properties [4]. More recently, the aforementioned
peptide cores were further designed to contain positively charged and aromatic
residues exposed at key exposed positions in order to additionally promote DNA
condensation and cell internalization. The results demonstrate that these
designer peptide fibrils can act as CPP (Cell-Penetrating Peptides), can
efficiently enter mammalian cells while carrying packaged luciferase- encoding
plasmid DNA and act as a protein expression enhancers. Interestingly, the
peptides further exhibited strong antimicrobial activity against the
enterobacterium Escherichia coli [5].
Such short self-assembling peptides that are amenable to computational design
offer open-ended possibilities towards multifunctional bionanomaterial
scaffolds of the future [6].
**References **
1\. Tamamis, P., Kasotakis, E. Archontis, G. and Mitraki, A. (2014)
“Combination of experimental and theoretical approaches for the design and
study of fibril-forming peptides†in “Protein design: Methods and
applications, second edition†edited by Valentin Kohler, in Methods in
Molecular Biology series, Humana Press, Springer Science, NY, 1216: 53-70
2\. Deidda G. et al., Self-assembled amyloid peptides with Arg-Gly-Asp (RGD)
motifs as scaffolds for tissue engineering. ACS Biomaterials Sci. and
Engineering 3, (2017), 1404-1416
3\. Kokotidou C. et al., A Novel Amyloid Designable Scaffold and Potential
Inhibitor Inspired by GAIIG of Amyloid Beta and the HIV-1 V3 loop. FEBS
letters, (2018) 592 :1777-1788.
4\. Jonnalagadda SVR et al., Computational design of functional amyloid
materials with cesium binding, deposition and capture properties. J. Phys.
Chem. B. (2018) 122:7555-7568
5\. Kokotidou C. et al., Designer Amyloid Cell-Penetrating Peptides for
Potential Use as Gene Transfer Vehicles. (2020) Biomolecules 10 :7, DOI:
10.3390/biom10010007
6. Kokotidou, C., Tamamis, P. & Mitraki, A. (2020) “Amyloid-like peptide aggregates†“in “Peptide-based Biomaterials†edited by Mustafa O. Guler, The Royal Society of Chemistry series, pp. 217-268.
**Host:** E. Georgelis
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ONLINE nanoGUNE: Anna Mitraki; University Crete - CIC nanoGUNE
When: May 17, 2021 11:00 AM
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