Role of TRP channels as sensors of mechanical alterations in the plasma membrane

The survival of organisms relies on the constant monitoring of the chemical environment. The first step in chemo-sensation is classically understood as direct binding of compounds to receptor proteins. However, recent evidence suggests that this process may be also based on the detection of mechanical alterations induced by molecules on the plasma membrane. We hypothesize that the sensory functions of Transient Receptor Potential cation channels, an emerging family of chemosensors, are determined by direct effects of chemical stimuli on the membrane lipid environment. To test this, we will implement a new mathematical model of channel-membrane-chemical interactions to explore the relationship between TRP channel functions and the dynamics of membrane lipids. As experimental counterpart, we will use several biophysical methods to determine whether the activation of the broadly-tuned chemo-sensor TRPA1 correlates with the alteration of thermodynamic properties of the lipid bilayer. Finally, we will explore the relevance of the channel-membrane interaction hypothesis in broader perspective, by evaluating the effects of extracellular lipid vesicles on TRP channels and the consequences of these interactions on cell signalling processes. This project will shed light on the molecular mechanisms underlying unconventional chemosensory processes that are relevant for animal adaptation and toxicology, and may help in the design strategies for the treatment of chemically-induced injury.