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Research Directions - Floudas Group
The main research interests of Prof. G. Floudas are on biopolymer self-assembly and dynamics, as well as on nano-structured polymers and liquid crystals.
Biopolymers as scaffolds for tissue engineering
Nature employs simple and elegant molecular tools and mechanisms to synthesize soft and hard tissues with unique properties and functions. Of key importance in this process of molecular engineering is the combination of building blocks with controlled self-assembly in a hierarchical manner from the nano- to the macroscale. In this process, proteins and polypeptides are employed as the main molecular building blocks that combine the ability to self-assemble with molecular recognition and genetic manipulation. Polypeptides, in particular, have been the subject of intensive studies because of their vital role in molecules designed for use in drug delivery of gene therapy. Their two main ordered local conformations (i.e., secondary structures), namely, α-helices stabilized by intra-molecular hydrogen bonds and β-strand conformations stabilized through inter-molecular hydrogen bonds, offer an additional means to direct self-assembly.
The ability to control, predict and ultimately manipulate the peptide secondary structure represents the ultimate goal of this research. In particular, we need to understand how the chemical tailoring of the structure of oligopeptides, polypeptides and oligopeptide-base molecular hybrids affects their self-assembly and activity. The availability of model synthetic peptide copolymers with well defined secondary structures may provide compounds that would allow establishing structure-activity relationships which could lead to the design of more effective peptide drugs.
The ability of homopolypeptides to undergo conformational changes due to environmental changes such as pH, temperature, ionic strength is well known. What is less known, is the persistence length of the different secondary structures as well as the origin of their complex dynamic behavior. Model oligo- and polypeptides offer the possibility of controlled conditions where these issues can be addressed.
Going into more complex systems, like polypeptide-based rod-coil copolymers, it is natural to expect that their rather unusual self-assembling behaviour has to be determined by the delicate (competitive or synergetic) combination of intra- and intermoleculer interactions. These include the possibility to organize supramolecular assemblies with the propensity to form a reversible hydrogen-bond network of a-helical and b-strand secondary structures in the rigid rod-like polypeptide block, on one hand, and, the statistical nature of synthetic random-coil polymers on the other hand. Due to its weakness, hydrogen bonding allows additional freedom to control the strength of bonding, e.g., by temperature or solvent. Also, it is known that the superb performance of biological polypeptide-based materials such as hair or spiders' silk is due to a hierarchical superstructure with several length scales where structure control is exerted at every level of hierarchy. Different experimental techniques are needed to explore the hierarchical self-assembly at the different length and time-scales. An example of the different methods that have been employed by our group (in collaboration with the NMR group at the Max-Planck Institute for Polymer Research) are depicted in Figure 1.
Figure 1. Assembly of a lamellar forming polypeptide-coil diblock copolymer depicting the main techniques employed in identifying the hierarchy of structures: Small-angle X-ray scattering (SAXS) is employed for the domain spacing, d. 13C NMR and wide-angle X-ray scattering (WAXS) are employed to identify the type of the peptide secondary structure (α-helical in the schematic). WAXS is further employed to get the lateral self-assembly of α-helices within the polypeptide domain (a hexagonal lattice is indicated in the schematic). Dielectric spectroscopy (DS) and site-specific NMR techniques are employed for the dynamics. Furthermore, the most intense DS process (Fig. 2) provides the persistence length, ξ, of α-helical segments.
In addition to self-assembly, we are exploring the polypeptide dynamics (Figure 2). Since the helical conformation of polypeptides is built by regular intramolecular hydrogen bonds between the N-H and C=O groups, there is a direct addition of residual dipole components along the polymer chain giving rise to a huge dipole moment. This dipole moment is attractive for two reasons. First, it allows studying the local and global polypeptide dynamics and the associated dynamic arrest at the liquid-to-glass transition (a transition that in proteins inhibits biological activity) and the solvent-induced “slaving” of polypeptides and protein dynamics. Second, polar poly(γ-benzyl-l-glutamate) (PBLG) molecules can spontaneously form a polar packing structure in their lyotropic solution. This finding is important since a similar polarity packing may possible arise in the self-organized structure of biological helical proteins and its electrical properties such as ferroelectricity and piezoelectricity may serve in living systems.
