Beom Jin Kim

Cytoprotective Alginate/Polydopamine Core/Shell Microcapsules in Microbial Encapsulation

Chemical encapsulation of microbes in threedimensional polymeric microcapsules promises various applications, such as cell therapy and biosensors, and provides a basic platform for studying microbial communications. However, the cytoprotection of microbes in the microcapsules against external aggressors has been a major challenge in the field of microbial microencapsulation, because ionotropic hydrogels widely used for microencapsulation swell uncontrollably, and are physicochemically labile. Herein, we developed a simple polydopamine coating for obtaining cytoprotective capability of the alginate capsule that encapsulated Saccharomyces cerevisiae. The resulting alginate/ polydopamine core/shell capsule was mechanically tough, prevented gel swelling and cell leakage, and increased resistance against enzymatic attack and UV-C irradiation. We believe that this multifunctional core/shell structure will provide a practical tool for manipulating microorganisms inside the microcapsules.

Cytocompatible Polymer Grafting from Individual Living Cells by Atom-Transfer Radical Polymerization

A cytocompatible method of surface-initiated, activator regenerated by electron transfer, atom transfer radical polymerization (SI-ARGET ATRP) is developed for engineering cell surfaces with synthetic polymers. Dopamine-based ATRP initiators are used for both introducing the ATRP initiator onto chemically complex cell surfaces uniformly (by the material-independent coating property of polydopamine) and protecting the cells from radical attack during polymerization (by the radical-scavenging property of polydopamine). Synthetic polymers are grafted onto the surface of individual yeast cells without significant loss of cell viability, and the uniform and dense grafting is confirmed by various characterization methods including agglutination assay and cell-division studies. This work will provide a strategic approach to the generation of living cell-polymer hybrid structures and open the door to their application in multitude of areas, such as sensor technology, catalysis, theranostics, and cell therapy.

Magnetotactic molecular architectures from self-assembly of β-peptide foldamers

The design of stimuli-responsive self-assembled molecular systems capable of undergoing mechanical work is one of the most important challenges in synthetic chemistry and materials science. Here we report that foldectures, that is, self-assembled molecular architectures of β-peptide foldamers, uniformly align with respect to an applied static magnetic field, and also show instantaneous orientational motion in a dynamic magnetic field. This response is explained by the amplified anisotropy of the diamagnetic susceptibilities as a result of the well-ordered molecular packing of the foldectures. In addition, the motions of foldectures at the microscale can be translated into magnetotactic behaviour at the macroscopic scale in a way reminiscent to that of magnetosomes in magnetotactic bacteria. This study will provide significant inspiration for designing the next generation of biocompatible peptide-based molecular machines with applications in biological systems.

Biphasic Supramolecular Self-Assembly of Ferric Ions and Tannic Acid across Interfaces for Nanofilm Formation

Cell nanoencapsulation provides a chemical tool for the isolation and protection of living cells from harmful, and often lethal, external environments. Although several strategies are available to form nanometric films, most methods heavily rely on time-consuming multistep processes and are not biocompatible. Here, the interfacial supramolecular self-assembly and film formation of ferric ions (FeIII ) and tannic acid (TA) in biphasic systems is reported, where FeIII and TA come into contact each other and self-assemble across the interface of two immiscible phases. The interfacial nanofilm formation developed is simple, fast, and cytocompatible. Its versatility is demonstrated with various biphasic systems: hollow microcapsules, encasing microbial or mammalian cells, that are generated at the water-oil interface in a microfluidic device; a cytoprotective FeIII -TA shell that forms on the surface of the alginate microbead, which then entraps probiotic Lactobacillus acidophilus; and a pericellular FeIII -TA shell that forms on individual Saccharomyces cerevisiae. This biphasic interfacial reaction system provides a simple but versatile structural motif in materials science, as well as advancing chemical manipulability of living cells.

Artificial Spores: Immunoprotective Nanocoating of Red Blood Cells with Supramolecular Ferric Ion-Tannic Acid Complex

The blood-type-mismatch problem, in addition to shortage of blood donation, in blood transfusion has prompted the researchers to develop universal blood that does not require blood typing. In this work, the “cell-in-shell” (i.e., artificial spore) approach is utilized to shield the immune-provoking epitopes on the surface of red blood cells (RBCs). Individual RBCs are successfully coated with supramolecular metal-organic coordination complex of ferric ion (FeIII) and tannic acid (TA). The use of isotonic saline (0.85% NaCl) is found to be critical in the formation of stable, reasonably thick (20 nm) shells on RBCs without any aggregation and hemolysis. The formed “RBC-in-shell” structures maintain their original shapes, and effectively attenuate the antibody-mediated agglutination. Moreover, the oxygen-carrying capability of RBCs is not deteriorated after shell formation. This work suggests a simple but fast method for generating immune-camouflaged RBCs, which would contribute to the development of universal blood.

Control of Microbial Growth in Alginate/Polydopamine Core/Shell Microbeads

Microbial microencapsulation not only protects microorganisms from harmful environments by physically isolating them from the outside media but also has the potential to tailor the release profile of the encapsulated cells. However, the microbial release has not yet been controlled tightly, leading to undesired detrimental exposure of microorganisms to the outside. In this work, we suggest a simple method for controlling the cell release by suppressing the microbial growth in the microbeads. Alginate microbeads, encapsulating yeast cells, were coated with ultrathin but robust polydopamine shells, and the resulting core/shell structures effectively reduced the growth rate, while maintaining the cell viability.

Modulation of Heterotypic and Homotypic Cell-Cell Interactions via Zwitterionic Lipid Masks

Since the pioneering work by Whitesides, innumerable platforms that aim to spatio-selectively seed cells and control the degree of cell-cell interactions in vitro have been developed. These methods, however, have generally been technically and methodologically complex, or demanded stringent materials and conditions. In this work, we introduce zwitterionic lipids as patternable, cell-repellant masks for selectively seeding cells. The lipid masks are easily removed with a routine washing step under physiological conditions (37 °C, pH 7.4), and are used to create patterned cocultures, as well as to conduct cell migration studies. We demonstrate, via patterned cocultures of NIH 3T3 fibroblasts and HeLa cells, that HeLa cells proliferate far more aggressively than NIH 3T3 cells, regardless of initial population sizes. We also show that fibronectin-coated substrates induce cell movement akin to collective migration in NIH 3T3 fibroblasts, while the cells cultured on unmodified substrates migrate independently. Our lipid mask platform offers a rapid and highly biocompatible means of selectively seeding cells, and acts as a versatile tool for the study of cell-cell interactions.

Enzymatic film formation of nature-derived phenolic amines

An enzyme-instructed method is developed for material-independent, cytocompatible coating of phenolic amines, inspired by melanogenesis found in nature. Tyrosinase-based film formation proceeds smoothly in an aqueous solution at neutral pH, and can use various phenolic amines including catecholamines, such as tyrosine, tyramine, dopamine, norepinephrine, and DOPA, as a coating precursor. Compared with polydopamine coating, the method is fast and efficient, and forms uniform films. Its high cytocompatibility is advantageously applied to cell-surface engineering, where chemically labile Jurkat cells are coated individually without any noticeable decrease in viability. Considering the huge potential of polyphenolic-based coatings, the strategy developed herein will provide an advanced tool for manipulating biological entities, including living cells, in biomedical and medicinal applications.

Salt-Induced, Continuous Deposition of Supramolecular Iron(III)–Tannic Acid Complex

One-step assembly of iron(III)-tannic acid (Fe3+-TA) complex forms nanothin (∼10 nm) films on various substrates within minutes. In this deposition scheme, however, the film does not grow continuously over time even though Fe3+-TA complex is still abundant in the coating solution. In this paper, we report that the salt addition dramatically changes the one-off coating characteristic to continuous one, and each salt has its optimum concentration ( CMFT) that produces maximum film thickness. For detailed investigation of the salt effects, we employed various salts, including LiCl, NaCl, KCl, CaCl2, SrCl2, BaCl2, NaBr, and NaNO3, and found that only cations played an important role in the continuous deposition of the Fe3+-TA complex, with smaller CMFT values for the cations of higher valency and larger size. On the basis of the results, we suggested that the positively charged cations screened the negative surface charges of Fe3+-TA complex particles, leading to coagulation and continuous deposition, further supported by the ζ-potential measurement and time-resolved dynamic light-scattering analysis.

Pioneering Effects and Enhanced Neurite Complexity of Primary Hippocampal Neurons on Hierarchical Neurotemplated Scaffolds

In this work, the use of scaffolds is reported, templated from live neurons as an advanced culture platform for primary neurons. Hippocampal neurons cultured on neurotemplated scaffolds exhibit an affinity for templated somas, revealing a preference for micrometric structures amidst nanotopographical features. It is also reported, for the first time, that neurite complexity can be topographically controlled by increasing the density of nanometric features on neurotemplated scaffolds. Neurotemplated scaffolds are versatile, hierarchical topographies that feature biologically relevant structures, in both form and scale, and capture the true complexity of an in vivo environment. The introduction and implementation of neurotemplated scaffolds is sure to advance research in the fields of neurodevelopment, network development, and neuroregeneration.