Molecularly informed field theory for estimating critical micelle concentrations of intrinsically disordered protein surfactants.

The critical micelle concentration (CMC) is a crucial parameter in understanding the self-assembly behavior of surfactants. In this study, we combine simulation and experiment to demonstrate the predictive capability of molecularly informed field theories in estimating the CMC of biologically based protein surfactants. Our simulation approach combines the relative entropy coarse-graining of small-scale atomistic simulations with large-scale field-theoretic simulations, allowing us to efficiently compute the free energy of micelle formation necessary for the CMC calculation while preserving chemistry-specific information about the underlying surfactant building blocks. We apply this methodology to a unique intrinsically disordered protein platform capable of a wide variety of tailored sequences that enable tunable micelle self-assembly. The computational predictions of the CMC closely match experimental measurements, demonstrating the potential of molecularly informed field theories as a valuable tool to investigate self-assembly in bio-based macromolecules systematically.

Electrostatic Conjugation of Nanoparticle Surfaces with Functional Peptide Motifs.

We report the surface functionalization of anionic layer by layer nanoparticles (LbL NPs) with cationic tumor-penetrating peptides (TPPs) via electrostatic adsorption while retaining particle stability and charge characteristics. This strategy eliminates the need for structural modifications of the peptide and enables facile functionalization of surface chemistries difficult to modify or inaccessible via covalent conjugation strategies. We show that both carboxylated and sulfated LbL NPs are able to accommodate linear and cyclic TPPs and used fluorescence-based detection assays to quantify peptide loading per NP. We also demonstrate that TPP activity is retained upon adsorption, implying sufficient numbers of peptides take on the appropriate surface orientation, enabling efficient uptake of functionalized NPs in vitro, as characterized via flow cytometry and deconvolution microscopy. Overall, we believe that this strategy will serve as a broadly applicable approach to impart electrostatically assembled NPs with bioactive peptide motifs.