Conjugated polymers mediate effective activation of the Mammalian Ion Channel Transient Receptor Potential Vanilloid 1

F Lodola,M R Antognazza,G Tullii,N Martino,G Lanzani

doi:10.1038/s41598-017-08541-6

Abstract

Selective and rapid regulation of ionic channels is pivotal to the understanding of physiological processes and has a crucial impact in developing novel therapeutic strategies. Transient Receptor Potential (TRP) channels are emerging as essential cellular switches that allow animals to respond to their environment. In particular, the Vanilloid Receptor 1 (TRPV1), besides being involved in the body temperature regulation and in the response to pain, has important roles in several neuronal functions, as cytoskeleton dynamics, injured neurons regeneration, synaptic plasticity. Currently available tools to modulate TRPV1 activity suffer from limited spatial selectivity, do not allow for temporally precise control, and are usually not reversible, thus limiting their application potential. The use of optical excitation would allow for overcoming all these limitations. Here, we propose a novel strategy, based on the use of light-sensitive, conjugated polymers. We demonstrate that illumination of a polymer thin film leads to reliable, robust and temporally precise control of TRPV1 channels. Interestingly, the activation of the channel is due to the combination of two different, locally confined effects, namely the release of thermal energy from the polymer surface and the variation of the local ionic concentration at the cell/polymer interface, both mediated by the polymer photoexcitation.

Highlights

Overall, the ensemble of the recent experimental evidences justifies the high interest for both activating and inhibiting agents of TRPV1, as novel physiological probes and powerful pharmacological targets
We demonstrate that illumination of the polymer leads to reliable, robust and temporally precise control of TRPV1 channel activity
P3HT is characterized by a wide optical absorption spectrum peaking at 520 nm (Fig. 1b), excellent optoelectronic properties when used as the active, light absorbing and charge generating material in solar cells and organic photodetectors[30] and outstanding biocompatibility properties when used in combination with living cells, as recently demonstrated in both in vitro and in vivo studies[31,32,33,34]

Summary

Introduction

The ensemble of the recent experimental evidences justifies the high interest for both activating and inhibiting agents of TRPV1, as novel physiological probes and powerful pharmacological targets. Two different, light activated methods have been proposed, based on the use either of photoswitchable compounds[28], composed by capsaicin derivatives linked to azobenzene molecules, or of light sensitive nanoparticles with high photothermal conversion efficiency[29]. Both of them exploited the synergistic combination of visible light with specific stimuli, fatty acids activators and heat, respectively. The activation of the channel can be interpreted on the base of the combined action of two different effects, both of them localized at the polymer surface: the release of thermal energy from the excited photoactive material, and the variation of the ionic concentration in the cleft niche, mediated by photoexcitation and accumulation of photo-generated negative charges at the interface between the polymer and the extracellular bath

Methods

Results

Conclusion