Dissertation Defense: David Cho
Candidate Name: David Cho
Major: Chemistry
Thesis Advisor: Jong-in Hahm, Ph.D.
Title: Fundamentals of Protein Adsorption and Assembly on Nano-Patterned Block Copolymers at the Single Molecule Level
Protein adsorption onto polymer surfaces is a very complex and ubiquitous phenomenon whose integrated process impacts essential applications in our daily life such as food packaging materials, health devices, diagnostic tools, and medical products. Increasingly, novel polymer materials with greater chemical intricacy and reduced dimensionality are used for various applications involving adsorbed proteins on their surfaces. Hence, the nature of protein–surface interactions to consider is becoming much more complicated than before. A large body of literature exists for protein adsorption. However, most of these investigations have focused on collectively measured, ensemble-averaged protein behaviors that occur on macroscale and chemically unvarying polymer surfaces instead of direct measurements at the single protein or sub-protein level. In addition, interrogations of protein–polymer adsorption boundaries in these studies were typically carried out by indirect methods, whose insights may not be suitably applied for explaining individual protein adsorption processes occurring onto nanostructured, chemically varying polymer surfaces.
Therefore, an important gap in our knowledge still exists that needs to be systematically addressed via direct measurement means at the single protein and sub-protein level. Such efforts will require multifaceted experimental and theoretical approaches that can probe multilength scales of protein adsorption, while encompassing both single proteins and their collective ensemble behaviors at the length scale spanning from the nanoscopic all the way to the macroscopic scale.
In this regard, I repeatedly and faithfully tracked individual proteins on the same nanodomain areas of a block copolymer (BCP) surface and monitor the adsorption and assembly behavior of a model protein, immunoglobulin G (IgG), over time into a tight surface-packed structure. With discrete protein adsorption events unambiguously visualized at the biomolecular level, the detailed assembly and packing states of IgG on the BCP nanodomain surface are
subsequently correlated to various regimes of IgG adsorption kinetic plots. Intriguing features, entirely different from those observed from macroscopic homopolymer templates, are identified from the IgG adsorption isotherms on the nanoscale, chemically varying BCP surface. This work not only provides much needed, direct experimental evidence for time-resolved, single protein level, adsorption events on nanoscale polymer surfaces but also signifies mutual linking between specific topographic states of protein adsorption and assembly to particular segments of adsorption isotherms. From the fundamental research viewpoint, the correlative ability to examine the nanoscopic surface organizations of individual proteins and their local as well as global adsorption kinetic profiles will be highly valuable for accurately determining protein assembly mechanisms and interpreting protein adsorption kinetics on nanoscale surfaces. Application-wise, such knowledge will also be important for fundamentally guiding the design and development of biomaterials and biomedical devices that exploit nanoscale polymer architectures.