Assembly of a patchy protein into variable 2D lattices via tunable multiscale interactions

Abstract

Self-assembly of molecular building blocks into higher-order structures is exploited in living systems to create functional complexity and represents a powerful strategy for constructing new materials. As nanoscale building blocks, proteins offer unique advantages, including monodispersity and atomically tunable interactions. Yet, control of protein self-assembly has been limited compared to inorganic or polymeric nanoparticles, which lack such attributes. Here, we report modular self-assembly of an engineered protein into four physicochemically distinct, precisely patterned 2D crystals via control of four classes of interactions spanning Ångström to several-nanometer length scales. We relate the resulting structures to the underlying free-energy landscape by combining in-situ atomic force microscopy observations of assembly with thermodynamic analyses of protein-protein and-surface interactions. Our results demonstrate rich phase behavior obtainable from a single, highly patchy protein when interactions acting over multiple length scales are exploited and predict unusual bulk-scale properties for protein-based materials that ensue from such control.

Protein Needles Designed to Self‐Assemble through Needle Tip Engineering

“…[13][14][15] More recently, high-speed AFM (HS-AFM) has been developed as a tool to directly visualize the dynamic behavior of proteins at the single molecule level and a time scale of sub-100 ms. [16] Due to the high spatiotemporal resolution, HS-AFM has enabled investigations of the growth kinetics of amyloid fibers, cell surface layer proteins, and other crystalline proteins. [17][18][19][20] However, direct observation of the anisotropic motion of proteins during formation of the assembly pattern has not been achieved because the proteins have symmetric structures, and sizes below the resolution limit of measurement techniques. There have been very few attempts to elucidate the assembly mechanism from the dynamic behavior of individual proteins.…”

Arrow of Time, Entropy, and Protein Folding: Holistic View on Biochirality

“…It is a common belief that studying the molecular mechanism of protein folding, from the original (unfolded) homochiral polypeptide chain to native conformation, has represented one of the biggest challenges in biochemistry and molecular biology [ 109 , 110 , 111 , 112 , 113 ]. In this field, the most intense debates were and remain focused on the role of entropy in protein self-assembly, into nano and mesoscale structures [ 107 , 108 , 109 ].…”

Organizing Multi-Enzyme Systems into Programmable Materials for Biocatalysis

“…In addition, impressive progress has been made in the design and construction of self-assembling protein nanostructures that can form the foundation of new types of materials for biocatalysis [83,109,[130][131][132][133][134][135]. Recent publications demonstrate the design of diverse protein nanostructures including cages, layers, crystals, and filaments [136][137][138][139][140][141], the engineering of a preexisting cage into various structures [142][143][144][145], the assembly of computationally designed icosahedral nanostructures [137,138], 2D-arrays, crystals [146,147], and protein filaments [81], as well as the design of metal-coordination, disulfide bridges, and surface electrostatics for the creation of functional 2D-lattices and cages [146,[148][149][150][151][152].…”