Self‐Assembly of Short Peptide Amphiphiles: The Cooperative Effect of Hydrophobic Interaction and Hydrogen Bonding

Abstract

The interplay between hydrogen bonding, hydrophobic interaction and the molecular geometry of amino acid side-chains is crucial to the development of nanostructures of short peptide amphiphiles. An important step towards developing their practical use is to understand how different amino acid side-chains tune hydrophobic interaction and hydrogen bonding and how this process leads to the control of the size and shape of the nanostructures. In this study, we have designed and synthesized three sets of short amphiphilic peptides (I(3)K, LI(2)K and L(3)K; L(3)K, L(4)K and L(5)K; I(3)K, I(4)K and I(5)K) and investigated how I and L affected their self-assembly in aqueous solution. The results have demonstrated a strong tendency of I groups to promote the growth of β-sheet hydrogen bonding and the subsequent formation of nanofibrillar shapes. All I(m)K (m = 3-5) peptides assembled into nanofibers with consistent β-sheet conformation, whereas the nanofiber diameters decreased as m increased due to geometrical constraint in peptide chain packing. In contrast, L groups had a weak tendency to promote β-sheet structuring and their hydrophobicity became dominant and resulted in globular micelles in L(3)K assembly. However, increase in the number of hydrophobic sequences to L(5)K induced β-sheet conformation due to the cooperative hydrophobic effect and the consequent formation of long nanofibers. The assembly of L(4)K was, therefore, intermediate between L(3)K and L(5)K, similar to the case of LI(2)K within the set of L(3)K, LI(2)K and I(3)K, with a steady transition from the dominance of hydrophobic interaction to hydrogen bonding. Thus, changes in hydrophobic length and swapping of L and I can alter the size and shape of the self-assembled nanostructures from these simple peptide amphiphiles.

Redox modulated hydrogelation of a self-assembling short peptide amphiphile

“…As shown in Figure 1, the N-and C-termini of the peptides were acetylated and amidated, respectively, to eliminate the effect of terminal charges that are believed to complicate the process of selfassembly. The detailed procedures have been described in our previous work [30][31][32][33]. Deprotection, activation, coupling and capping were carried out on the synthesizer and cleavage from the resin was finished manually away from the synthesizer.…”

Peptide self-assembly into lamellar phases and the formation of lipid-peptide nanostructures

“…Above a critical aggregation concentration (CAC), amphiphiles selfassemble into supramolecular structures similar to lipid mesophases. Several one-dimensional (1D) and two-dimensional (2D) structures have been reported, including micelles, cylinders, and lamellar or hexagonal phases [6][7][8][9][10][11][12][13][14][15][16][17]. Not only do peptides structurally resemble lipid molecules, but they also exhibit similar surfactant-like properties.…”

Polymers in Tissue Engineering

“…Varying the quantity and pattern of repeating ionic amino acid residues will change the mechanical properties [7]; however, longer peptides does not necessarily mean stronger peptides [8] so a proper balance between interacting molecules and unwieldy size must be struck. Much like varying the quantity of charged amino acid residues, varying the length of the hydrophobic and hydrophilic components of an amphiphilic molecule will change the degree of interaction between molecules, and vary the mechanical properties and structure of the hydrogel [9,10]. The concentration of the peptide in solution will also affect the amount of molecular interaction, and thus an increase in peptide concentration will usually increase the storage modulus of a hydrogel [4,11].…”