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ABSTRACT: BACKGROUND: A major challenge when creating interfaces for the nervous system is to translate between the signal carriers of the nervous system (ions and neurotransmitters) and those of conventional electronics (electrons). SCOPE OF REVIEW: Organic conjugated polymers represent a unique class of materials that utilizes both electrons and ions as charge carriers. Based on these materials, we have established a series of novel communication interfaces between electronic components and biological systems. The organic electronic ion pump (OEIP) presented in this review is made of the polymer-polyelectrolyte poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS). The OEIP translates electronic signals into electrophoretic migration of ions and neurotransmitters. MAJOR CONCLUSIONS: We demonstrate how spatio-temporally controlled delivery of ions and neurotransmitters can be used to modulate intracellular Ca(2+) signaling in neuronal cells in the absence of convective disturbances. The electronic control of delivery enables strict control of dynamic parameters, such as amplitude and frequency of Ca(2+) responses, and can be used to generate temporal patterns mimicking naturally occurring Ca(2+) oscillations. To enable further control of the ionic signals we developed the electrophoretic chemical transistor, an analogue of the traditional transistor used to amplify and/or switch electronic signals. Finally, we demonstrate the use of the OEIP in a new "machine-to-brain" interface by modulating brainstem responses in vivo. GENERAL SIGNIFICANCE: This review highlights the potential of communication interfaces based on conjugated polymers in generating complex, high-resolution, signal patterns to control cell physiology. We foresee widespread applications for these devices in biomedical research and in future medical devices within multiple therapeutic areas.
Biochimica et Biophysica Acta 12/2012; · 4.66 Impact Factor
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Biochimica et Biophysica Acta 03/2011; 1810(3):237-8. · 4.66 Impact Factor
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Advanced Materials 07/2009; 21(44):4442 - 4446. · 13.88 Impact Factor
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ABSTRACT: Cells and tissues use finely regulated ion fluxes for their intra- and intercellular communication. Technologies providing spatial and temporal control for studies of such fluxes are however, limited. We have developed an electrophoretic ion pump made of poly(3,4-ethylenedioxythiophene) doped with poly(styrene sulphonate) (PEDOT:PSS) to mediate electronic control of the ion homeostasis in neurons. Ion delivery from a source reservoir to a receiving electrolyte via a PEDOT:PSS thin-film channel was achieved by electronic addressing. Ions are delivered in high quantities at an associated on/off ratio exceeding 300. This induces physiological signalling events that can be recorded at the single-cell level. Furthermore, miniaturization of the device to a 50-microm-wide channel allows for stimulation of individual cells. As this technology platform allows for electronic control of ion signalling in individual cells with proper spatial and temporal resolution, it will be useful in further studies of communication in biological systems.
Nature Material 10/2007; 6(9):673-9. · 32.84 Impact Factor
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ABSTRACT: Bacterial pathogens produce a variety of exotoxins, which often become associated with the bacterial outer membrane component lipopolysaccharide (LPS) during their secretion. LPS is a potent proinflammatory mediator; however, it is not known whether LPS contributes to cell signaling induced by those microbial components to which it is attached. This is partly due to the common view that LPS present in bacterial component preparations is an experimental artifact. The Escherichia coli exotoxin hemolysin (Hly) is a known inducer of proinflammatory signaling in epithelial cells, and the signal transduction pathway involves fluctuation of the intracellular-Ca(2+) concentration. Since LPS is known to interact with Hly, we investigated whether it is required as a cofactor for the activity of Hly. We found that the LPS/Hly complex exploits the CD14/LPS-binding protein recognition system to bring Hly to the cell membrane, where intracellular-Ca(2+) signaling is initiated via specific activation of the small GTPase RhoA. Hly-induced Ca(2+) signaling was found to occur independently of the LPS receptor TLR4, suggesting that the role of LPS/CD14 is to deliver Hly to the cell membrane. In contrast, the cytolytic effect triggered by exposure of cells to high Hly concentrations occurs independently of LPS/CD14. Collectively, our data reveal a novel molecular mechanism for toxin delivery in bacterial pathogenesis, where LPS-associated microbial compounds are targeted to the host cell membrane as a consequence of their association with LPS.
Infection and Immunity 03/2007; 75(2):997-1004. · 4.16 Impact Factor
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ABSTRACT: An organic electronic ion pump, including poly(3,4-ethylenedioxythiophene) as the active material has been used to electronically control the transport of protons between two electrolytes and to change the pH of the target solution from 7 to 3 in a few minutes. The number of transported protons equals the time-integrated current between the two addressing electrodes. If no voltage is applied the leakage due to diffusion is not detectable, which indicates an overall proton delivery on/off ratio exceeding 1000. Locally, the pH drop can be even larger and the relationship between the proton delivery rate of the pump and proton diffusion in the electrolyte forms pH gradients. If the device is instead addressed with short pulses, local pH oscillations are created. The transport of protons presented here can be extended to other small sized ions, which in combination with the biocompatibility of the delivery surface make the device promising for cell communication studies and lab-on-a-chip applications.
Organic Electronics 9(3):303-309. · 4.05 Impact Factor
