Pilnam Kim

Nanoscale cues regulate the structure and function of macroscopic cardiac tissue constructs

Heart tissue possesses complex structural organization on multiple scales, from macro- to nano-, but nanoscale control of cardiac function has not been extensively analyzed. Inspired by ultrastructural analysis of the native tissue, we constructed a scalable, nanotopographically controlled model of myocardium mimicking the in vivo ventricular organization. Guided by nanoscale mechanical cues provided by the underlying hydrogel, the tissue constructs displayed anisotropic action potential propagation and contractility characteristic of the native tissue. Surprisingly, cell geometry, action potential conduction velocity, and the expression of a cell–cell coupling protein were exquisitely sensitive to differences in the substratum nanoscale features of the surrounding extracellular matrix. We propose that controlling cell–material interactions on the nanoscale can stipulate structure and function on the tissue level and yield novel insights into in vivo tissue physiology, while providing materials for tissue repair.

Hierarchical folding of elastic membranes under biaxial compressive stress

Mechanical instabilities that cause periodic wrinkling during compression of layered materials find applications in stretchable electronics and microfabrication, but can also limit an applications performance owing to delamination or cracking under loading and surface inhomogeneities during swelling. In particular, because of curvature localization, finite deformations can cause wrinkles to evolve into folds. The wrinkle-to-fold transition has been documented in several systems, mostly under uniaxial stress. However, the nucleation, the spatial structure and the dynamics of the invasion of folds in two-dimensional stress configurations remain elusive. Here, using a two-layer polymeric system under biaxial compressive stress, we show that a repetitive wrinkle-to-fold transition generates a hierarchical network of folds during reorganization of the stress field. The folds delineate individual domains, and each domain subdivides into smaller ones over multiple generations. By modifying the boundary conditions and geometry, we demonstrate control over the final network morphology. The ideas introduced here should find application in the many situations where stress impacts two-dimensional pattern formation.

Fabrication of nanostructures of polyethylene glycol for applications to protein adsorption and cell adhesion

A simple method was developed to fabricate polyethylene glycol (PEG) nanostructures using capillary lithography mediated by ultraviolet (UV) exposure. Acrylate-containing PEG monomers, such as PEG dimethacrylate (PEG-DMA, MW = 330), were photo-cross-linked under UV exposure to generate patterned structures. In comparison to unpatterned PEG films, hydrophobicity of PEG nanostructure modified surfaces was significantly enhanced. This could be attributed to trapped air in the nanostructures as supported by water contact angle measurements. Proteins (fibronectin, immunoglobulin, and albumin) and cells (fibroblasts and P19 EC cells) were examined on the modified surfaces to test for the level of protein adsorption and cell adhesion. It was found that proteins and cells preferred to adhere on nanostructured PEG surfaces in comparison to unpatterned PEG films; however, this level of adhesion was significantly lower than that of glass controls. These results suggest that capillary lithography can be used to fabricate PEG nanostructures capable of modifying protein and cell adhesive properties of surfaces.

Nanopatterned cardiac cell patches promote stem cell niche formation and myocardial regeneration.

Stem cell-based methods for myocardial regeneration suffer from considerable cell attrition. Artificial matrices reproducing mechanical and structural properties of the native tissue may facilitate survival, retention and functional integration of adult stem or progenitor cells, by conditioning the cells prior to, and during, transplantation. Here we combined autologous cardiosphere-derived cells (CDCs) with nanotopographically defined hydrogels mimicking the native myocardial matrix, to form in vitro cardiac stem cell niches, and control cell function and fate. These platforms were used to produce cardiac patches that could be transplanted at the site of infarct. In culture, highly anisotropic, but not more randomized nanotopographic, control augmented cell adhesion, migration, and proliferation. It also dramatically enhanced early, and, in the presence of mature cardiomyocytes, late cardiomyogenesis. Nanotopography sensing and transcriptional response was mediated via p190RhoGAP. In a rat infarction model, engraftment of nanofabricated scaffolds with CDCs enhanced retention and growth of transplanted cells, and their integration with the host tissue. The infarcted ventricle wall increased in thickness, with higher cell viability and better collagen organization. These results suggest that nanostructured polymeric materials that closely mimic the extracellular matrix structure on which cardiac cells reside in vivo can be both very effective tools in investigating the mechanisms of cardiac differentiation and the basis for cardiac tissue engineering, thus facilitating stem cell-based therapy in the heart.

Two-minute assembly of pristine large-area graphene based films.

We report a remarkably rapid method for assembling pristine graphene platelets into a large area transparent film at a liquid surface. Some 2-3 layer pristine graphene platelets temporally solvated with N-methyl-2-pyrrolidone (NMP) are assembled at the surface of a dilute aqueous suspension using an evaporation-driven Rayleigh-Taylor instability and then are driven together by Marangoni forces. The platelets are fixed through physical binding of their edges. Typically, 8-cm-diameter circular graphene films are generated within two minutes. Once formed, the films can be transferred onto various substrates with flat or textured topologies. This interfacial assembly protocol is generally applicable to other nanomaterials, including 0D fullerene and 1D carbon nanotubes, which commonly suffer from limited solution compatibility.

Soft lithographic patterning of supported lipid bilayers onto a surface and inside microfluidic channels

We present simple soft lithographic methods for patterning supported lipid bilayer (SLB) membranes onto a surface and inside microfluidic channels. Micropatterns of polyethylene glycol (PEG)-based polymers were fabricated on glass substrates by microcontact printing or capillary moulding. The patterned PEG surfaces have shown 97 +/- 0.5% reduction in lipid adsorption onto two dimensional surfaces and 95 +/- 1.2% reduction inside microfluidic channels in comparison to glass control. Atomic force microscopy measurements indicated that the deposition of lipid vesicles led to the formation of SLB membranes by vesicle fusion due to hydrophilic interactions with the exposed substrate. Furthermore, the functionality of the patterned SLBs was tested by measuring the binding interactions between biotin (ligand)-labeled lipid bilayer and streptavidin (receptor). SLB arrays were fabricated with spatial resolution down to approximately 500 nm on flat substrate and approximately 1 microm inside microfluidic channels, respectively.

Large‐Area Dual‐Scale Metal Transfer by Adhesive Force

We report a large-area, dual-scale metal transfer method by using a difference in adhesive force. Rigiflex polyurethane acrylate (PUA) molds with engraved nanoscale patterns were used to transfer metal layers (Au or Al) to flexible polyethylene terephthalate (PET) substrate. Transfer process was performed sequentially for the metal layers on ridge and valley regions of the mold, resulting in a dual-scale metal transfer from a single master. A simple metal wire grid polarizer was fabricated and analyzed using this method.

Capillary kinetics of thin polymer films in permeable microcavities

We present a Poiseuille model that can explain the rate of capillary rise of thin polymer films in permeable microcavities. In comparison to the traditional Poiseuille formulation, two features of the system were considered: the permeable nature of the enclosure and the effect of thin polymer films that are confined to the substrate. The model predicts that the rate is inversely proportional to the channel width, contrary to what the original Poiseuille model predicts, and it is proportional to the initial film thickness, which the original model cannot account for. The modified model is in satisfactory agreement with experimental data.

Stepwise Self‐Assembly of a Protein Nanoarray from a Nanoimprinted Poly(Ethylene Glycol) Hydrogel

This work was supported by Core Research for Evolutional Science and Technology (CREST) of Japan Science and Technology Agency (JST), and New Energy and Industrial Technology Development Organization (NEDO).

Wrinkle-Directed Self-Assembly of Block Copolymers for Aligning of Nanowire Arrays

Highly aligned metal nanowire arrays with feature sizes approaching 10 nm are fabricated. This is made possible by the self-assembly of block copolymers (BCPs) on graphene-wrinkle arrays. Thickness-modulated BCP films confined on the wrinkled reduced graphene oxide (rGO) surface promote the strict alignment of the self-assembled BCP lamellae in the direction of the film thickness gradient.