Haeshin Lee

Single-molecule mechanics of mussel adhesion.

The glue proteins secreted by marine mussels bind strongly to virtually all inorganic and organic surfaces in aqueous environments in which most adhesives function poorly. Studies of these functionally unique proteins have revealed the presence of the unusual amino acid 3,4-dihydroxy-l-phenylalanine (dopa), which is formed by posttranslational modification of tyrosine. However, the detailed binding mechanisms of dopa remain unknown, and the chemical basis for mussels’ ability to adhere to both inorganic and organic surfaces has never been fully explained. Herein, we report a single-molecule study of the substrate and oxidation-dependent adhesive properties of dopa. Atomic force microscopy (AFM) measurements of a single dopa residue contacting a wet metal oxide surface reveal a surprisingly high strength yet fully reversible, noncovalent interaction. The magnitude of the bond dissociation energy as well as the inability to observe this interaction with tyrosine suggests that dopa is critical to adhesion and that the binding mechanism is not hydrogen bond formation. Oxidation of dopa, as occurs during curing of the secreted mussel glue, dramatically reduces the strength of the interaction to metal oxide but results in high strength irreversible covalent bond formation to an organic surface. A new picture of the interfacial adhesive role of dopa emerges from these studies, in which dopa exploits a remarkable combination of high strength and chemical multifunctionality to accomplish adhesion to substrates of widely varying composition from organic to metallic.

A reversible wet/dry adhesive inspired by mussels and geckos

The adhesive strategy of the gecko relies on foot pads composed of specialized keratinous foot-hairs called setae, which are subdivided into terminal spatulae of approximately 200 nm (ref. 1). Contact between the gecko foot and an opposing surface generates adhesive forces that are sufficient to allow the gecko to cling onto vertical and even inverted surfaces. Although strong, the adhesion is temporary, permitting rapid detachment and reattachment of the gecko foot during locomotion. Researchers have attempted to capture these properties of gecko adhesive in synthetic mimics with nanoscale surface features reminiscent of setae; however, maintenance of adhesive performance over many cycles has been elusive, and gecko adhesion is greatly diminished upon full immersion in water. Here we report a hybrid biologically inspired adhesive consisting of an array of nanofabricated polymer pillars coated with a thin layer of a synthetic polymer that mimics the wet adhesive proteins found in mussel holdfasts. Wet adhesion of the nanostructured polymer pillar arrays increased nearly 15-fold when coated with mussel-mimetic polymer. The system maintains its adhesive performance for over a thousand contact cycles in both dry and wet environments. This hybrid adhesive, which combines the salient design elements of both gecko and mussel adhesives, should be useful for reversible attachment to a variety of surfaces in any environment.

General functionalization route for cell adhesion on non-wetting surfaces

We present a versatile route for promoting cell adhesion and viability on various non-wetting surfaces, inspired by mussel adhesion mechanism. The oxidative polymerization of dopamine, a small designer molecule of the DOPA-K motif found in mussels, results in the formation of a poly(dopamine) ad-layer on any material surface. We found that the poly(dopamine) coating can promote cell adhesion on any type of material surfaces including the well-known anti-adhesive substrate, poly(tetrafluoroethylene). According to our results, mammalian cells well adhered and underwent general cell adhesion processes (i.e., attachment to substrate, spreading, and cytoskeleton development) on poly(dopamine)-modified surfaces, while they barely adhered and spread on unmodified non-wetting surfaces. The mussel-inspired surface functionalization strategy is extremely useful because it does not require the time-consuming synthesis of complex linkers and the process is solvent-free and non-toxic. Therefore, it can be a powerful route for converting a variety of bioinert substrates into bioactive ones.

Mussel‐Inspired Adhesive Binders for High‐Performance Silicon Nanoparticle Anodes in Lithium‐Ion Batteries

Conjugation of mussel-inspired catechol groups to various polymer backbones results in materials suitable as silicon anode binders. The unique wetness-resistant adhesion provided by the catechol groups allows the silicon nanoparticle electrodes to maintain their structure throughout the repeated volume expansion and shrinkage during lithiation cycling, thus facilitating substantially improved specific capacities and cycle lives of lithium-ion batteries.

One-step modification of superhydrophobic surfaces by a mussel-inspired polymer coating.

A bio-inspired approach for superhydrophobic surface modification was investigated. Hydrophilic conversion of the superhydrophobic surface was easily achieved through this method, and the superhydrophobic-hydrophilic alternating surface was generated by the method combined with soft-lithography. The resulting patterned surface showed high water adhesion property in addition to superhydrophobic property.

Catechol-Functionalized Chitosan/Pluronic Hydrogels for Tissue Adhesives and Hemostatic Materials

Bioinspired from adhesion behaviors of mussels, injectable and thermosensitive chitosan/Pluronic composite hydrogels were synthesized for tissue adhesives and hemostatic materials. Chitosan conjugated with multiple catechol groups in the backbone was cross-linked with terminally thiolated Pluronic F-127 triblock copolymer to produce temperature-sensitive and adhesive sol-gel transition hydrogels. A blend mixture of the catechol-conjugated chitosan and the thiolated Pluronic F-127 was a viscous solution state at room temperature but became a cross-linked gel state with instantaneous solidification at the body temperature and physiological pH. The adhesive chitosan/Pluronic injectable hydrogels with remnant catechol groups showed strong adhesiveness to soft tissues and mucous layers and also demonstrated superior hemostatic properties. These chitosan/Pluronic hydrogels are expected to be usefully exploited for injectable drug delivery depots, tissue engineering hydrogels, tissue adhesives, and antibleeding materials.

Mussel-inspired encapsulation and functionalization of individual yeast cells.

The individual encapsulation of living cells has a great impact on the area of cell-based sensors and devices as well as fundamental studies in cell biology. In this work, living yeast cells were individually encapsulated with functionalizable, artificial polydopamine shells, inspired by an adhesive protein in mussels. Yeast cells maintained their viability within polydopamine, and the cell cycle was controlled by the thickness of the shells. In addition, the artificial shells aided the cell in offering much stronger resistance against foreign aggression, such as lyticase. After formation of the polydopamine shells, the shells were functionalized with streptavidin by utilizing the chemical reactivity of polydopamine, and the functionalized cells were biospecifically immobilized onto the defined surfaces. Our work suggests a biomimetic approach to the encapsulation and functionalization of individual living cells with covalently bonded, artificial shells.

Norepinephrine: Material-Independent, Multifunctional Surface Modification Reagent

A facile approach for material-independent surface modification using norepinephrine was investigated. pH-induced oxidative polymerization of norepinephrine forms adherent films on vastly different types of material surfaces of noble metals, metal oxides, semiconductors, ceramics, shape-memory alloys, and synthetic polymers. Secondary biochemical functionalizations such as immobilization of proteins and growth of biodegradable polyester on the poly(norepinephrine) films were demonstrated.

Polydopamine-mediated surface modification of scaffold materials for human neural stem cell engineering

Surface modification of tissue engineering scaffolds and substrates is required for improving the efficacy of stem cell therapy by generating physicochemical stimulation promoting proliferation and differentiation of stem cells. However, typical surface modification methods including chemical conjugation or physical absorption have several limitations such as multistep, complicated procedures, surface denaturation, batch-to-batch inconsistencies, and low surface conjugation efficiency. In this study, we report a mussel-inspired, biomimetic approach to surface modification for efficient and reliable manipulation of human neural stem cell (NSC) differentiation and proliferation. Our study demonstrates that polydopamine coating facilitates highly efficient, simple immobilization of neurotrophic growth factors and adhesion peptides onto polymer substrates. The growth factor or peptide-immobilized substrates greatly enhance differentiation and proliferation of human NSCs (human fetal brain-derived NSCs and human induced pluripotent stem cell-derived NSCs) at a level comparable or greater than currently available animal-derived coating materials (Matrigel) with safety issues. Therefore, polydopamine-mediated surface modification can provide a versatile platform technology for developing chemically defined, safe, functional substrates and scaffolds for therapeutic applications of human NSCs.

Thermo-sensitive, injectable, and tissue adhesive sol–gel transition hyaluronic acid/pluronic composite hydrogels prepared from bio-inspired catechol-thiol reaction

Hyaluronic acid (HA) hydrogels are widely pursued as tissue regenerative and drug delivery materials due to their excellent biocompatibility and biodegradability. Inspired by mussel adhesion, we report here a novel class of thermo-sensitive and injectable HA/Pluronic F127 composite tissue-adhesive hydrogels applicable for various biomedical applications. HA conjugated with dopamine (HA-DN) was mixed with thiol end-capped Pluronic F127 copolymer (Plu-SH) to produce a lightly cross-linked HA/Pluronic composite gel structure based on Michael-type catechol-thiol addition reaction. The HA/Pluronic hydrogels exhibited temperature-dependent sol–gel phase transition behaviors different from Pluronic hydrogels. Rheological studies showed that the sol–gel transitions were rapid and reversible in response to temperature. The HA/Pluronic hydrogels could be injected in vivo in a sol state at room temperature using a syringe, but immediately became a robust gel state at body temperature. The in situ formed hydrogels exhibited excellent tissue-adhesion properties with superior in vivo gel stability and are potentially useful for drug and cell delivery.