Deciphering the mechanisms of 1D and 2D self-assembly of biopolymers

Abstract

Self-assembled biomolecular architectures have exhibited various properties, including electronic, optical, chemical, and mechanical. Due to their diverse structures and unique functions, hierarchical biomolecular assemblies have found a wide range of potential applications in materials science, biomedical engineering, tissue engineering, or nanotechnology. These appealing properties have intensified interest in understanding their design and structural control, and great advances have been achieved. However, little attention has been given to the mechanism by which they nucleate and grow. Understanding the dominant pathways and parameters determining their pathway selection, as well as the formation kinetics, would enable precise control over phase and morphology during the synthesis of these biomolecular nanostructures. Here, we first introduce recent studies of biomolecular self-assembly and key factors controlling their assemblies, followed by a brief discussion about the functionalization of these materials and their applications. Then we present our study on a two-dimensional (2D) peptide assembly system. Using a peptide selected for its binding affinity to MoS2 surfaces, we directly observed nucleation and growth of 2D arrays by molecularly resolved in situ atomic force microscopy (AFM) and compared the results to molecular dynamics (MD) simulations. We find the peptide arrays exhibit an epitaxial relationship to the underlying lattice but assemble one row at a time from dimeric structural units. The nuclei are ordered from the earliest stages and form without a nucleation free energy barrier, a result predicted by classical nucleation theory for one-dimensional (1D) crystals. Moreover, aspect ratios of the arrays can be tuned simply via peptide concentration. We also reveal the effects of peptide sequences and substrates on the assembly pathway. Furthermore, we demonstrate several peptoid designs to mimic the behaviors of the original peptide sequence and seek for potential applications. Based on the developed approaches, the assembly and disassembly of 1D and 2D computationally designed proteins were also investigated. In the case of the helical filament system where protein monomers were designed to assemble into 1D fibers, growth kinetics were carefully studied, and the growth rate was found to have a linear dependency on monomer concentration. Accessory capping units triggered the dissolution of fibers and showed an asymmetric disassembly behavior from two different ends. In the last part, we show the co-assembly of two designed proteins into 2D honeycomb lattices. We studied their edge structures and verified the rate-determining step. The self-assembling systems studied here share similar features with many other reported self-assembling systems. Our study on their nucleation and growth may provide a guide for interpreting and controlling their assembly and provide new strategies for their future design.