Role of Hydrophobicity on Self-Assembly by Peptide Amphiphiles via Molecular Dynamics Simulations

Abstract

Using a novel coarse-grained model, large-scale molecular dynamics simulations were performed to examine self-assembly of 800 peptide amphiphiles (sequence palmitoyl-V3A3E3). Under suitable physiological conditions, these molecules readily assemble into nanofibers leading to hydrogel construction as observed in experiments. Our simulations capture this spontaneous self-assembly process, including formation of secondary structure, to identify morphological transitions of distinctive nanostructures. As the hydrophobic interaction is increased, progression from open networks of secondary structures toward closed cylindrical nanostructures containing either β-sheets or random coils are observed. Moreover, temperature effects are also determined to play an important role in regulating formation of secondary structures within those nanostructures. These understandings of the molecular interactions involved and the role of environmental factors on hydrogel formation provide useful insight for development of innovative smart biomaterials for biomedical applications.

Sequence-Dependent Structural Stability of Self-Assembled Cylindrical Nanofibers by Peptide Amphiphiles

“…As the β-sheet forming peptide region become less hydrophobic as in the case of PA4, the ability to form stable one-dimensional nanofiborus structure with contiguous hydrophobic core is limited. This agrees with our previous studies that examine the effects of solventdependent hydrophobicity 44,45 and to some extent pHdependent electrostatics 10,42 on PA self-assembly.…”

Molecular simulations of peptide amphiphiles

“…Overall, in order for the formation of elongated cylindrical nanofibers, Velichko et al suggests that β-sheet formation acts as the nucleation step followed by the cooperative effect of hydrogen bonding between peptide segments and the hydrophobic collapse of alkyl tails. These results are also supported by recent CG simulation studies by Fu et al 82 as shown in Figure 3B that suggests with increasing hydrophobicity, PAs first aggregate into a network of β-sheets and then assemble into cylindrical nanofibers followed by cylindrical micelles. The necessity of β-sheets for cylindrical nanofiber assembly was further explored by a comparative study of two cylindrical nanofibers composed with two PA monomers (Alanine rich and Valine rich).…”

“…In the last decade, an increasing number of computational groups have provided major insights into the structure and self-assembly of PA nanofibers as shown in Table 1 and in discussed within the context of this review. 8,20–33 …”

Computational Amphiphilic Materials for Drug Delivery

“…A phase diagram between electrostatics and temperature was constructed shown in Figure 13 for the delineating morphological regions in response to external stimuli (Fu et al, 2013). In terms of hydrophobicity, they observed the progressive transition from open network to closed cylindrical structure with increasing hydrophobicity (Fu et al, 2014). Furthermore, they examined solvent effects on peptide assembly.…”