Engineering self-assembly of giant molecules in the condensed state based on molecular nanoparticles.

In biological systems, it is well-known that the activities and functions of biomacromolecules are dictated not only by their primary chemistries, but also by their secondary, tertiary, and quaternary hierarchical structures. Achieving control of similar levels in synthetic macromolecules is yet to be demonstrated. Most of the critical molecular parameters associated with molecular and hierarchical structures, such as size, composition, topology, sequence, and stereochemistry, are heterogenous, which impedes the exploration and understanding of structure formation and manipulation. Alternatively, in the past few years we have developed a unique giant molecule system based on molecular nanoparticles, in which the above-mentioned molecular parameters, as well as interactions, are precisely defined and controlled. These molecules could self-assemble into a myriad of unconventional and unique structures in the bulk, thin films, and solution. Giant molecules thus offer a robust platform to manipulate the hierarchical structures via precise and modular assemblies of building blocks in an amplified size level compared with small molecules. It has been found that they are not only scientifically intriguing, but also technologically relevant.

Three-Dimensional Ordered Antibody Arrays Through Self-Assembly of Antibody-Polymer Conjugates.

Three-dimensional (3D) ordered arrays of human immunoglobulin G (IgG) were fabricated using well-defined full-length antibody-polymer conjugates (APCs). The conjugates were prepared through a two-step sequential click approach with a combination of oxime ligation and strain promoted alkyne-azide cycloaddition. They were able to self-assemble into lamellar nanostructures with alternating IgG and poly(N-isopropylacrylamide) (PNIPAM) nanodomains. As a proof-of-concept, these materials were fabricated into thin films and their specific binding ability was tested. The nanostructure not only improves the packing density and the proper orientation of the IgG, but also provides nanochannels to facilitate substrate transport.

Pathway toward large two-dimensional hexagonally patterned colloidal nanosheets in solution.

We report the solution self-assembly of an ABC block terpolymer consisting of a polystyrene-block-poly(ethylene oxide) (PS-b-PEO) diblock copolymer tail tethered to a fluorinated polyhedral oligomeric silsesquioxane (FPOSS) cage in 1,4-dioxane/water. With increasing water content, abundant unconventional morphologies, including circular cylinders, two-dimensional hexagonally patterned colloidal nanosheets, and laterally patterned vesicles, are sequentially observed. The formation of toroids is dominated by two competing free energies: the end-cap energy of cylinders and the bending energy to form the circular structures. Incorporating the superhydrophobic FPOSS cages enhances the end-cap energy and promotes toroid formation. Lateral aggregation and fusion of the cylinders results in primitive nanosheets that are stabilized by the thicker rims to partially release the rim-cap energy. Rearrangement of the parallel-aligned FPOSS cylindrical cores generates hexagonally patterned nanosheets. Further increasing the water content induces the formation of vesicles with nanopatterned walls.

Protein-Polymer Block Copolymer Thin Films for Highly Sensitive Detection of Small Proteins in Biological Fluids.

In nearly all biosensors, sensitivity is greatly reduced for measurements conducted in biological matrices due to nonspecific binding from off-target molecules. One method to overcome this issue is to design a sensor that enables selective size-based uptake of proteins. Herein, a protein-polymer conjugate thin-film biosensor is fabricated that self-assembles into lamellae containing alternating domains of protein and polymer. Analyte is captured in protein regions while polymer domains restrict diffusion of large molecules. Device sensitivity and size-based exclusion properties are probed using two analytes: streptavidin (SA, 52.8 kDa) and monomeric streptavidin (mSA2, 15.6 kDa). Tuning domain spacing by adjusting polymer molecular weight allows the design of films that relatively freely uptake mSA2 and largely restrict SA diffusion. Furthermore, when detecting the smaller mSA2, no reduction in the limit of detection (LOD) is observed when transitioning from detection in the buffer to detection in biological fluids. As a result, LOD measured in fluid samples is reduced by 2 orders of magnitude compared to a traditional surface-immobilized protein monolayer.