Computational Reverse-Engineering Analysis for Scattering Experiments (CREASE) on the Self-Assembly of Amphiphilic Polymer-peptide Conjugates

Assembly of peptide-based amphiphilic polymer chains in solution provides a route for the design of materials for a variety of applications (e.g., drug delivery vesicles). The engineering of these materials depends on the precise characterization of the assembled structures, often obtained through small angle scattering techniques. The interpretation of these scattering profiles typically relies on analytical models for conventional shapes that may not capture the system geometry at hand. This calls for a method that can tie scattering profile features directly to molecular details in complex nanostructures without needing off-the-shelf scattering models. To address this need, we apply recent extensions of Computational Reverse-Engineering Analysis for Scattering Experiments (CREASE) to a system of polymer-peptide conjugates that self-assemble into bilayer and vesicle structures. Taking in scattering intensity profiles and polymer chemistries as inputs, CREASE combines genetic algorithm and molecular reconstruction simulations to determine the peptide amphiphile bilayer composition, vesicle dimensions (e.g. core diameter, layer thicknesses) and molecular level packing within the nanostructure.