A Protonic Biotransducer for Controlling ATP Synthesis in Mitochondria

Abstract

Controlling the flow of ions and electrons at the device/biological interface has become an important challenge in broad fields such as bioelectronics and medical biology. These devices provide a new way to translate bidirectionally between the ionic language of biology and the electronic language of circuitry. The current strategy to develop such ion and electron controlling devices is to use new functional materials at the device/biological interface. For example, silicon nanowire and carbon nanotube based transistors use ions to read out biological functions. Aluminum nanostraws and carbon nanotube porins can selectively deliver molecules such as cations, DNA, and nicotine into biological materials. Since conductive polymers allow the transport of both ions and electrons, there are many conductive polymer based examples including organic field effect transistors for biosensing and organic ion pumps for locally delivering ions and neurotransmitters into cells and the brain. Along with ions and small molecules, protons (H+) play an important role in biology. Examples include the homeostatic pH regulation in body and bacteria, acid sensing ion channels activating in neuron cells, proton activated bioluminescence in dinoflagellates, and pH responsive flagella in bacteria. Mitochondria in particular are a noteworthy organelle that utilize the transport of protons and electrons across a membrane to synthesize adenosine triphosphate (ATP) molecules. To translate H+ signals from biological environments into measureable electronic signals, Rolandi and co-workers developed a prototype bioprotonic device using a Pd/PdHx protode. In his group, the metallic protode was used to measure the protonic conductivity in biological materials such as chitosan and jelly from in the ampullae of Lorenzini of sharks, and to integrate electronic signals with an enzymatic flip flop circuit, ion channels, and light-sensitive bacteriorhodopsin. Gorodestky and co-workers have separately demonstrated high proton conductivity in reflectin squid proteins and Pd/PdHx based transistors. All attempts however focused on the interfacing between Pd-based metal and biological materials, even though the Pd protode may occur side reactions such as oxygen conversion (PdO, PdO2 and Pd(OH)x) at the potentials beginning at 0.9 V vs. NHE and toxic hydrogen peroxide production. Here, we develop an organic biotransducer using a high H+-coupling conductive polymer of sulfonated polyaniline (SPA) that monitors and modulates the pH in the vicinity of the SPA electrode, even in solutions with the high buffering capacity typical of mitochondrial environments (Fig.1). We integrate this biotransducer with mitochondria isolated from pig hearts to translate the H+ signal from the activated mitochondria into a measureable protonic current, and also to control the activity of ATP synthase through electrochemical pH modulation at the SPA surface. Figure 1