Assembly and Dynamics of Random Heteropolymers in Aqueous Environments*

Biological systems require immense complexity to sustain their inherent processes, but understanding and applying each of their intricacies to synthetic systems is extremely challenging. Synthetic random heteropolymers (RHPs) have recently been shown to capture the behaviors of proteins in biological environments by acting as ensembles with varying segmental properties. We hypothesize that RHPs can also leverage their side chain heterogeneity to capture the arrangements of proteins in time and space. We thus apply scattering techniques coupled with computational sequence analysis to probe the effects of segmental heterogeneity on RHP assembly and dynamics in solution. Our results indicate that in the absence of specific and monodisperse protein-like primary and secondary structures, RHPs can still achieve higher-order spatial correlations in aqueous environments. Owing to their methacrylate-based backbones, they retain sufficient backbone rigidity to allow exposed patches of chemically similar side chains to drive the assembly without unraveling at the single-chain level. These results provide fundamental insights into the use of randomness at the sequence level to achieve order at the chain level, while also defining the key parameters driving assembly tendencies seen in RHPs’ biological analogs.