Research Project: Amfifilik peptit Moloküllerinin Oluşturulduğu Nanofiberlerin ve Ağ Yapıların Oluşumu, Yapıları ve Kararlığı
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Contributors
Funders
ID
TB.00106
Authors
Sayar, Mehmet
Faculty Member
Publications
Role of hydrophobic/aromatic residues on the stability of double-wall β-sheet structures formed by a triblock peptide
(American Chemical Society, 2017) Özgür, Beytullah; Sayar, Mehmet; N/A; Department of Mechanical Engineering; Graduate School of Sciences and Engineering; Yes; College of Engineering; GRADUATE SCHOOL OF SCIENCES AND ENGINEERING
Bioinspited self-assembling peptides serve as powerful building blocks in the manufacturing of nanomaterials with tailored-featifreS, Because of their ease of synthesis, biocornpatibility, and tunable activity, this emerging branch of biomolecules has become very popular. the triblock peptide architecture designed by the Hartgerink group is a versatile system that allows control over its assembly and has been shown to demonstrate tunable-bioactivity. Three main forces, Coulomb repulsion, hydrogen bonding and hydrophobicity act together to guide the triblock peptides' assembly into one-dimensional objects and hydrogels. It was shown previously that both the nanofiber morphology-(e.g., intersheet- spacing, formation of antipaiallel/parallel beta-sheets) and,hydrogel theology strictly depend on the-choice of the core residue where the triblock peptide fibers with aromatic cores in general form shotterfibers-and yield poor hydrogels with respect to the ones with aliphatic cores. However, An elaborate understanding of-the molecular reasons behind: these changes remained unclear. in this study, by using carefully designed computer based free energy calculation, we' analyzed the influence of the core residue on the formation of double-wall fibers and single-Wall 6-sheets: Our results demonstrate that the aromatic substitution impairs the fiber cores and this impairment is "mainly-associated with a reduced hydrophobic character of the aromatic side chains. Such weakening is most obvious in tryp-tophan-containing peptides where the fiber core absorbs a. significant amount of water. We also show that the ability of tyrosine to form side :chain hydrogen bonds plays an indispensable role in the fiber stability. as opposed to the impairment of the fiber cores, single-wall P-sheets, with aromatic faces become more stable compared to the ones with aliphatic faces suggesting that the choice of the core residue can also affect the underlying assembly mechanism. We also provide an in-depth comparison, of competing structures (zero dimensional aggregates, short and long fibers) in the triblock peptides' assembly and show that, by adjusting the length of the terminal blocks,, the fiber growth can be turned on or off-while keeping the nanofiber morphology intact.
Assembly of triblock amphiphilic peptides into one-dimensional aggregates and network formation
(amer Chemical Soc, 2016) Özgür, Beytullah; Sayar, Mehmet; N/A; Department of Mechanical Engineering; Graduate School of Sciences and Engineering; Yes; College of Engineering; GRADUATE SCHOOL OF SCIENCES AND ENGINEERING
Peptide assembly plays a key role in both neurological diseases and development of novel biomaterials with well-defined nanostructures. Synthetic model peptides provide a unique platform to explore the role of intermolecular interactions in the assembly process. a triblock peptide architecture designed by the Hartgerink group is a versatile system which relies on Coulomb interactions, hydrogen bonding, and hydrophobicity to guide these peptides' assembly at three different length scales: beta-sheets, double-wall ribbon-like aggregates, and finally a highly porous network structure which can support gels with <= 1% by weight peptide concentration. in this study, by using molecular dynamics simulations of a structure based implicit solvent coarse grained model, we analyzed this hierarchical assembly process. Parametrization of our CG model is based on multiple-state points from atomistic simulations, which enables this model to represent the conformational adaptability of the triblock peptide molecule based on the surrounding medium. Our results indicate that emergence of the double-wall beta-sheet packing mechanism, proposed in light of the experimental evidence, strongly depends on the subtle balance of the intermolecular forces. We demonstrate that, even though backbone hydrogen bonding dominates the early nucleation stages, depending on the strength of the hydrophobic and Coulomb forces, Alternative structures such as zero-dimensional aggregates with two beta-sheets oriented orthogonally (which we refer to as a cross-packed structure) and beta-sheets with misoriented hydrophobic side chains are also feasible. We discuss the implications of these competing structures for the three different length scales of assembly by systematically investigating the influence of density, counterion valency, and hydrophobicity.
