Peptide Self-Assembled Nanostructures with Distinct Morphologies and Properties Fabricated by Molecular Design

Abstract

Six surfactant-like peptides with the same amino acid composition but different primary sequences are designed, including GAVIK, KIVAG, IVAGK, KGAVI, VGIAK, and KAIGV. These peptides form antiparallel β-sheets during self-assembly. Because the constituent residues have different side chain size and hydrophobicity, sequence changes adjust group distribution and hydrophobicity on the two sides of a given β-sheet. This consequently tunes the binding energy of the side-to-side pairing conformations and leads to different self-assembled structures. GAVIK and KIVAG form short nanorods with diameters of 8.5 ± 1.0 nm and lengths <150 nm. IVAGK and KGAVI form nanosheets with heights of 4.0 ± 0.5 nm and limited lengths and widths. VGIAK and KAIGV form long fibrils with diameters of 7.0 ± 1.0 nm and lengths of micrometer scale. These nanostructures exhibit different capacity in encapsulating insoluble hydrophobic drug molecules and delivering them into the cells. The nanosheets of IVAGK and KGAVI can encapsulate both nile red and doxorubicin molecules to an extent of up to 17-23% in mole ratio. Moreover, the shape and size of the nanostructures affect the drug delivery into cells greatly, with the nanosheets and short rods exhibiting higher efficiency than the long fibrils. The study provides new insights into programmed peptide self-assembly toward specific functionalities.

Guiding the Morphology of Amyloid Assemblies by Electrostatic Capping: from Polymorphic Twisted Fibrils to Uniform Nanorods

“…This result indicates that the neighboring sequence of an amyloid‐core affects the thermodynamic stability of the resulting assemblies, as previously observed for barnase‐related peptide fibrils . We also evaluated the critical aggregation concentration (CAC) of KI 10 using pyrene, a probe that is sensitive to the polarity of the local environment . A sharp transition from monomers to assemblies was observed when the concentration exceeded 33 × 10 −6 m (Figure d, Figure S7, Supporting Information).…”

“…CAC was determined by plotting the ratio of fluorescence intensity (373 nm/384 nm) as function of the concentration. Intersection of the two linear fits was used to determine the CAC …”

Control over the fibrillization yield by varying the oligomeric nucleation propensities of self-assembling peptides

“…toward the size distribution of the oligomeric particles and the thermodynamic stability of the fibrils are also evaluated, which helps defining the mechanism leading to the differential polymerization yield. Thereby, our study enhances our understanding of the important role of oligomeric intermediates in defining the outcome of self-assembly systems and advances the rational design principles of self-assembling peptides that give different supramolecular properties for a wide latitude of applications [2][3][4]44,45 . Moreover, our findings suggest that charged protein gatekeeper sequences 46 can prevent amyloidosis by lowering the size of the oligomeric particles.…”

“…In contrast, for applications that require the fibril infrastructure, e.g., for therapeutic scaffolds [2][3][4] , one should engineer the SLP with higher β-sheet propensities and lower number of charges to maximize the yield of fibril structures (like SLP1). In addition, for applications that use 1D nanofibers as reservoir for hydrophobic drug release 45 , the amount of micellar oligomer co-present in the system can affect the overall drug release profile. At last, with respect to protein aggregation, a previous genome-wide sequence analysis revealed that, in close proximity to the aggregation-prone β-strand regions in proteins, charged ''gatekeeper" residues often prevent the β-strand sequences from aggregating 46 .…”

Self-Assembly of Short Elastin-like Amphiphilic Peptides: Effects of Temperature, Molecular Hydrophobicity and Charge Distribution

“…Short amphiphilic peptides are one important category of self-assembling peptides that can form distinct nanostructures [36,37]. By having specific mechanistic property and high biocompatibility, these nanostructures show potential applications in vast areas including templates for nanostructure construction [38], scaffolds for tissue engineering [39,40], carriers for medicine delivery [41,42,43], and biological surface engineering [44,45]. It is of great interest to see whether we can develop temperature-responsive self-assembly molecules by involving the elastin β-turn units into the amphiphilic peptides.…”