Synthetic molecular communication (MC) is a new communication engineering paradigm which is expected to enable revolutionary applications such as smart drug delivery and real-time health monitoring. The design and implementation of synthetic MC systems (MCSs) at nano-and microscale is very challenging. This is particularly true for synthetic MCSs employing biological components as transmitters and receivers or as interfaces with natural biological MCSs. Nevertheless, since such biological components have been optimized by nature over billions of years, using them in synthetic MCSs is highly promising. This paper provides a survey of biological components that can potentially serve as the main building blocks, i.e., transmitter, receiver, and signaling particles, for the design and implementation of synthetic MCSs. Nature uses a large variety of signaling particles of different sizes and with vastly different properties for communication among biological entities. Here, we focus on three important classes of signaling particles: cations (specifically protons and calcium ions), neurotransmitters (specifically acetylcholine, dopamine, and serotonin), and phosphopeptides. These three classes have unique and distinct features such as their large diffusion coefficients, their specificity, and/or their uniqueness of signaling that make them suitable candidates for signaling particles in synthetic MCSs. For each of these candidate signaling particles, we present several specific transmitter and receiver structures mainly built upon proteins that are capable of performing the distinct physiological functionalities required from the transmitters and receivers of MCSs. Moreover, we present options for both microscale implementation of MCSs as well as the micro-to-macroscale interfaces needed for experimental evaluation of MCSs. One of the main advantages of employing proteins for signal emission and detection is that they can be modified with tools from synthetic biology and be tailored to a wide range of application needs. We discuss the properties, limitations, and applications of the proposed biological building blocks for synthetic MCSs in detail. Furthermore, we outline new research directions for the implementation and the theoretical design and analysis of the proposed transmitter and receiver architectures.

Pain, although unpleasant, is an essential warning mechanism against injury and damage of the organism. An intricate network of specialised sensors and transmission systems contributes to reception, transmission and central sensitization of pain. Here, we briefly introduce some of the main aspects of pain signal transmission, including nociceptors and nociceptive signals, mechanisms of inflammatory and neuropathic pain, and the situation of diabetes-associated neuropathic pain. The role of glia—astrocytes, microglia, satellite glia cells—and their specific channels, transporters and signaling pathways is described. A focus is on the contribution of inhibitory synaptic signaling to nociception and a possible role of glycine receptors in glucose-mediated analgesia and treatment-induced diabetic neuropathy. Inhibitory receptors such as GABA_A- and glycine receptors are important contributors to nociceptive signaling; their contribution to altered pain sensation in diabetes may be of clinical relevance, and they could be promising therapeutic targets towards the development of novel analgesics.

The inhibitory glycine receptor (GlyR) is a key mediator of synaptic signaling in spinal cord, brain stem, and higher central nervous system regions. The flavonoids quercetin and genistein have been identified previously as promising GlyR antagonists in vitro, but their detailed mechanism of action was not known. Here, inhibition of recombinant human α1 GlyRs in HEK 293 cells by genistein, quercetin, and strychnine was studied using whole-cell recording techniques. The interaction of several inhibitors applied alone or in combination was analyzed using a minimum mechanism of receptor activation and inhibition. Receptor inhibition in vivo was studied in a mouse model of strychnine toxicity. Genistein, quercetin, and strychnine were noncompetitive GlyR inhibitors. The inhibitory potency of one flavonoid (either genistein or quercetin) was not affected by simultaneous application of the other, suggesting that both flavonoids target the same site on the receptor. In combination with strychnine, flavonoid inhibition was augmented, indicating that strychnine binds to a position on the receptor physically distant from the flavonoid site. Potentiation of strychnine inhibition by flavonoids was also observed in vivo, where harmless doses of flavonoids enhanced strychnine toxicity in mice. Thus, in vitro and in vivo studies demonstrated a true synergism between flavonoids and strychnine for GlyR inhibition. The mechanism-based approach used here allows a rapid analysis of the effects of single drugs versus drug combinations.