Computational Reverse-Engineering Analysis for Scattering Experiments (CREASE) Applied to Self-Assembled Polymer-peptide Conjugate Solutions*

Engineering amphiphilic polymers in solution gives rise to a wide range of applications such as drug delivery and hydrogels. The precise characterization of the self-assembled nanostructures (e.g. via small angle scattering techniques and microscopy) is key to the design of these materials with controllable morphologies. We apply recent extensions of Computational Reverse-Engineering Analysis for Scattering Experiments (CREASE) to quantify the bilayer and vesicle structures within self-assembled polymer-peptide conjugate solutions. CREASE takes in scattering intensity profiles and polymer chemistries as inputs for a genetic algorithm to determine the peptide amphiphile bilayer composition and vesicle dimensions (e.g. core diameter, layer thicknesses) and then feeds the outcome to molecular reconstruction simulations to access molecular level conformations within the nanostructure (e.g. radii of gyration, chain packing, monomer concentration profiles). This method ties scattering profile features directly to molecular details in complex nanostructures without the need for off-the-shelf scattering models and provides chain and monomer structural information that is difficult to obtain through scattering and microscopy alone.