Design of Peptide Hydrogels for Drug Delivery: An Experimental and Computational Study

Neetu Singh Yadav
Postdoctoral Researcher
Sarupria Group

Self-assembling peptide nanostructures have shown to be of great importance in nature and have many promising applications, for example, in medicine as drug delivery vehicles, biosensors and antivirals. There are numerous interesting candidate molecules within the sequence space built from the 20 amino acids. However, the immense complexity and variety spanned makes it difficult to screen and predict the supramolecular behavior merely based on sequence. Here, we employ a synergistic simulation and experimental approach that can be applied to explore the peptide space and identify peptides for drug delivery applications. These methods cover a broad range of length and time scales, from the very short (i.e., atomic level), via all-atom molecular dynamics (MD) simulations, up to the macroscopic one, via scanning electron microscopy (SEM) experiments. We explore the self-assembly of RAE, RAEF and ALKx (namely ALK1, ALK2 and ALK3) peptides in water. The circular dichroism (CD) spectra of peptides illustrates the beta sheet rich superstructures, whereas scanning electron microscopy (SEM) analysis shows the peptide morphology with several hundreds of nanometers of length. The MD simulation provides mechanistic insight into the crucial roles of hydrophilic and hydrophobic amino acids in the assembly of ALKx peptide derivatives; it reveals that assembly capability is reduced by increasing the length of hydrophilic Lys residues in ALKx peptides. Experiments and simulation results are in qualitative agreement. Based on various measures, the strength of the self-assembly propensity of the peptides in aqueous solutions attains the following order: ALK1=RAE>ALK2>ALK3>RAEF. Together this data provides insights into the mechanisms of self-assembly of model peptides. These results will enable bottom-up design of novel peptides for use in drug delivery.