The Impact of Molecular Sequence on Hierarchical Assembly of Biomimetic Polymers

Many macromolecules assemble into ordered structures along hierarchical pathways that begin with formation of amorphous or dense-liquid precursors. Whether these multi-step pathways are general features of macromolecules or a consequence of system-specific structural details is unknown. Moreover, the dynamics of such pathways are poorly understood. Using AFM to observe surface-directed assembly of sequence-defined polymers, we show that pathways are sequence dependent. While some sequences exhibit classical pathways with direct appearance of ordered structures, slight changes in sequence involving addition of hydrophobic groups lead to hierarchical pathways: disordered clusters 10-20 molecules in size first appear and eventually transform into ordered nuclei that then enter the growth phase. Predictions from kinetic models that consider competing rates of cluster formation, deposition and transformation agree with the observations and bound the magnitude of kinetic terms controlling assembly. Molecular dynamics combined with force spectroscopy reveals the role of hydrophobic groups and background electrolytes in driving multi-step pathways and altering nucleation kinetics. The results provide insights into structural and energetic controls on macromolecular assembly pathways.