Silicon Nanowires and Optical Stimulation for Investigations of Intra- and Intercellular Electrical Coupling.

Myofibroblasts can spontaneously internalize silicon nanowires (SiNWs), making them an attractive target for bioelectronic applications. These cell-silicon hybrids offer leadless optical modulation capabilities with minimal perturbation to normal cell behavior. The optical capabilities are obtained by the photothermal and photoelectric properties of SiNWs. These hybrids can be harvested using standard tissue culture techniques and then applied to different biological scenarios. We demonstrate here how these hybrids can be used to study the electrical coupling of cardiac cells and compare how myofibroblasts couple to one another or to cardiomyocytes. This process can be accomplished without special equipment beyond a fluorescent microscope with coupled laser line. Also shown is the use of a custom-built MATLAB routine that allows the quantification of calcium propagation within and between the different cells in the culture. Myofibroblasts are shown to have a slower electrical response than that of cardiomyocytes. Moreover, the myofibroblast intercellular propagation shows slightly slower, though comparable velocities to their intracellular velocities, suggesting passive propagation through gap junctions or nanotubes. This technique is highly adaptable and can be easily applied to other cellular arenas, for in vitro as well as in vivo or ex vivo investigations.

Recent advances in bioelectronics chemistry.

Research in bioelectronics is highly interdisciplinary, with many new developments being based on techniques from across the physical and life sciences. Advances in our understanding of the fundamental chemistry underlying the materials used in bioelectronic applications have been a crucial component of many recent discoveries. In this review, we highlight ways in which a chemistry-oriented perspective may facilitate novel and deep insights into both the fundamental scientific understanding and the design of materials, which can in turn tune the functionality and biocompatibility of bioelectronic devices. We provide an in-depth examination of several developments in the field, organized by the chemical properties of the materials. We conclude by surveying how some of the latest major topics of chemical research may be further integrated with bioelectronics.

Silicon Nanowires for Intracellular Optical Interrogation with Subcellular Resolution.

Current techniques for intracellular electrical interrogation are limited by substrate-bound devices, technically demanding methods, or insufficient spatial resolution. In this work, we use freestanding silicon nanowires to achieve photoelectric stimulation in myofibroblasts with subcellular resolution. We demonstrate that myofibroblasts spontaneously internalize silicon nanowires and subsequently remain viable and capable of mitosis. We then show that stimulation of silicon nanowires at separate intracellular locations results in local calcium fluxes in subcellular regions. Moreover, nanowire-myofibroblast hybrids electrically couple with cardiomyocytes in coculture, and photostimulation of the nanowires increases the spontaneous activation rate in coupled cardiomyocytes. Finally, we demonstrate that this methodology can be extended to the interrogation of signaling in neuron-glia interactions using nanowire-containing oligodendrocytes.

Biological Interfaces, Modulation, and Sensing with Inorganic Nano-Bioelectronic Materials.

The last several years have seen a large and increasing interest in scientific developments that combine methods and materials from nanotechnology with questions and applications in bioelectronics. This follows with a number of broader trends: the rapid increase in functionality for materials at the nanoscale; a growing recognition of the importance of electric fields in diverse physiological processes; and continuous improvements in technologies that are naturally complementary with bioelectronics, such as optogenetics. Here, a progress report is provided on several of the most exciting recent developments in this field. The three critical functions of biointerface formation, biological modulation, and biological sensing using newly developed nanoscale materials are considered.

Living myofibroblast-silicon composites for probing electrical coupling in cardiac systems.

Traditional bioelectronics, primarily comprised of nonliving synthetic materials, lack cellular behaviors such as adaptability and motility. This shortcoming results in mechanically invasive devices and nonnatural signal transduction across cells and tissues. Moreover, resolving heterocellular electrical communication in vivo is extremely limited due to the invasiveness of traditional interconnected electrical probes. In this paper, we present a cell-silicon hybrid that integrates native cellular behavior (e.g., gap junction formation and biosignal processing) with nongenetically enabled photosensitivity. This hybrid configuration allows interconnect-free cellular modulation with subcellular spatial resolution for bioelectric studies. Specifically, we hybridize cardiac myofibroblasts with silicon nanowires and use these engineered hybrids to synchronize the electrical activity of cardiomyocytes, studying heterocellular bioelectric coupling in vitro. Thereafter, we inject the engineered myofibroblasts into heart tissues and show their ability to seamlessly integrate into contractile tissues in vivo. Finally, we apply local photostimulation with high cell specificity to tackle a long-standing debate regarding the existence of myofibroblast-cardiomyocyte electrical coupling in vivo.

Force localization modes in dynamic epithelial colonies.

Collective cell behaviors, including tissue remodeling, morphogenesis, and cancer metastasis, rely on dynamics among cells, their neighbors, and the extracellular matrix. The lack of quantitative models precludes understanding of how cell-cell and cell-matrix interactions regulate tissue-scale force transmission to guide morphogenic processes. We integrate biophysical measurements on model epithelial tissues and computational modeling to explore how cell-level dynamics alter mechanical stress organization at multicellular scales. We show that traction stress distribution in epithelial colonies can vary widely for identical geometries. For colonies with peripheral localization of traction stresses, we recapitulate previously described mechanical behavior of cohesive tissues with a continuum model. By contrast, highly motile cells within colonies produce traction stresses that fluctuate in space and time. To predict the traction force dynamics, we introduce an active adherent vertex model (AAVM) for epithelial monolayers. AAVM predicts that increased cellular motility and reduced intercellular mechanical coupling localize traction stresses in the colony interior, in agreement with our experimental data. Furthermore, the model captures a wide spectrum of localized stress production modes that arise from individual cell activities including cell division, rotation, and polarized migration. This approach provides a robust quantitative framework to study how cell-scale dynamics influence force transmission in epithelial tissues.

Self-association of water-soluble peptoids comprising (S)-N-1-(naphthylethyl)glycine residues.

Peptoids (N-substituted glycine oligomers) are widely used peptidomimetics, and an enhanced understanding of their structures is needed to expand their utility, particularly in aqueous applications. We report the synthesis and structural study of four water-soluble peptoids that include strongly helix-promoting (S)-N-1-(naphthylethyl)glycine residues. Peptoid structure changes with both peptoid length and solvent composition. Multiple data support the self-association of the longest peptoid studied here, 1, via hydrophobic interactions in aqueous solutions.