BioE Graduate Seminars

Event Introduction

Rational design of self-assembling amyloid building blocks as scaffolds for novel biomaterials

Abstract

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 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. 

About the speaker

Anna Mitraki is Professor at the Department of Materials Science and Technology at the University of Crete and Affiliated Research Scientist at IESL-FORTH (since September 2004). She received her BS in Chemistry from the University of Thessaloniki, Greece, 1981 and her PhD in Biochemistry from the Université Paris-Sud, Orsay, France in 1986 (for work on enzyme folding, assembly and aggregation with Professor Jeannine Yon-Kahn). She subsequently was a post-doctoral associate at the Massachusetts Institute of Technology, Cambridge, MA, U.S.A. (1987-1991) and then a Research Scientist  (1991-1994) (work on folding and assembly of fibrous phage proteins with Professor Jonathan King). She received her Habilitation from the Université Joseph Fourier, Grenoble, France, in 2003 for work on structure, folding and assembly of beta-structured fibrous proteins and their self-assembling peptides. She worked as Research Scientist at the Institut de Biologie Structurale in Grenoble, France (French National Research Center) from 1995 to 2004. From 2004 to 2014 she was Associate Professor at the Materials Science and Technology Department at the University of Crete ; she was promoted to Professor in 2014. She has published more than 60 publications in peer-reviewed scientific journals that have been cited so far (February 2021) 3524 times, with h-index of 31 (Google Scholar).

 Anna Mitraki has been working for more than 30 years on the folding, assembly and structure of natural fibrous proteins. She got interested in using these proteins as models for the design of new fibrous materials. Her current research interests include: protein folding and assembly; protein engineering and production; design and study of fibrous biomaterials; self-assembling protein and peptide materials. She is particularly interested in translating fundamental structural knowledge from natural fibrous proteins into concrete integration strategies and applications in the area of fibrous bio-nano-materials. She especially focuses on the use of designer amyloid peptide materials as technological objects and their integration in innovative applications.