
Self-assembled macromolecular architectures exhibit a range of structural motifs such as particles, fibers, ribbons and sheets with functions that include selective transport, structural scaffolding, mineral templating, and protection from pathogenesis. Although the structure of the isolated molecules dictates their governing interactions, function emerges from the mesoscale organization that arises from assembly. In the classical picture of assembly, order develops concomitantly with condensation as part of the microscopic density fluctuations that are inherent to all systems. However, the establishment of long-range order in macromolecular structures almost always requires significant changes in conformation away from that seen in the monomeric state. Moreover, the presence of hydrophobic regions can drive aggregation events that compete with ordered assembly. The impact of such structural transformations and transient states on the assembly process are a current subject of intense research. Using in situ techniques including AFM, dynamic force spectroscopy and ATR FTIR, we have investigated the dynamics of assembly and intermolecular interactions for a number of natural protein and synthetic sequence-defined polymer systems assembling from solution on single crystal surfaces. In high molecular weight systems, the results show that conformational transformations impose kinetic limitations on the nucleation of order. Transient fluctuations no longer provide a pathway to order; instead, the system must be driven to stabilize amorphous or liquid-like precursors. Moreover, once the ordered structure nucleates within these precursors, conformational changes of the remaining solution-phase monomers are catalyzed by the presence of the ordered nucleus. However, the final architecture depends strongly on the interplay between protein-protein, protein-surface, and protein-solvent interactions. Moreover, small changes in sequence that alter the balance of hydrophobic and electrostatic interactions can induce a switch in assembly pathway between the multi-stage process described above and direct formation of the ordered structure. Finally, building 2D structures at interfaces out of molecules that assemble one row at a time, eliminates the barrier to nucleation and creates an asymmetry in nucleation kinetics for the first row and all subsequent rows, creating a simple means to tune the aspect ratio of the resulting 2D materials. The results of these studies suggest that the requirement of conformational transformation introduces a timescale for structural relaxation that differs from that of the density fluctuations and thus alters the pathway and kinetics of assembly, but that the details of macromolecular sequence, solvent interactions, and the architecture of the 2D crystal can be used to influence barriers, pathways and outcomes.

Self-assembled macromolecular architectures exhibit a range of structural motifs such as particles, fibers, ribbons and sheets with functions that include selective transport, structural scaffolding, mineral templating, and protection from pathogenesis. Although the structure of the isolated molecules dictates their governing interactions, function emerges from the mesoscale organization that arises from assembly. In the classical picture of assembly, order develops concomitantly with condensation as part of the microscopic density fluctuations that are inherent to all systems. However, the establishment of long-range order in macromolecular structures almost always requires significant changes in conformation away from that seen in the monomeric state. Moreover, the presence of hydrophobic regions can drive aggregation events that compete with ordered assembly. The impact of such structural transformations and transient states on the assembly process are a current subject of intense research. Using in situ techniques including AFM, dynamic force spectroscopy and ATR FTIR, we have investigated the dynamics of assembly and intermolecular interactions for a number of natural protein and synthetic sequence-defined polymer systems assembling from solution on single crystal surfaces. In high molecular weight systems, the results show that conformational transformations impose kinetic limitations on the nucleation of order. Transient fluctuations no longer provide a pathway to order; instead, the system must be driven to stabilize amorphous or liquid-like precursors. Moreover, once the ordered structure nucleates within these precursors, conformational changes of the remaining solution-phase monomers are catalyzed by the presence of the ordered nucleus. However, the final architecture depends strongly on the interplay between protein-protein, protein-surface, and protein-solvent interactions. Moreover, small changes in sequence that alter the balance of hydrophobic and electrostatic interactions can induce a switch in assembly pathway between the multi-stage process described above and direct formation of the ordered structure. Finally, building 2D structures at interfaces out of molecules that assemble one row at a time, eliminates the barrier to nucleation and creates an asymmetry in nucleation kinetics for the first row and all subsequent rows, creating a simple means to tune the aspect ratio of the resulting 2D materials. The results of these studies suggest that the requirement of conformational transformation introduces a timescale for structural relaxation that differs from that of the density fluctuations and thus alters the pathway and kinetics of assembly, but that the details of macromolecular sequence, solvent interactions, and the architecture of the 2D crystal can be used to influence barriers, pathways and outcomes.