Transient Receptor Potential Channels as Sensors of Extracellular Lipid Vesicles

Transient receptor potential (TRP) channels are ubiquitous molecular sensors of chemical, thermal and mechanical stimuli and are thereby involved in numerous physiological and pathophysiological processes and proposed as targets to treat multiple human diseases. TRP channels are activated by mechanical stimuli inducing shear stress and changes in membrane curvature and tension, and by the perturbations produced by insertion of chemicals in cell membranes. Based on previous studies by our group and solid preliminary data, we here hypothesize that TRP channels can sense the extracellular lipid vesicles upon their interaction with the plasma membrane of target cells. We will test this hypothesis by using a wide variety of up-to-date experimental techniques to: 1) screen the effects of multiple natural and artificial lipid vesicles on several sensory TRP channels, 2) study the ability of lipid vesicles to induce mechanical perturbations activating TRP channels and 3) determine the pathophysiological relevance of vesicle-TRP channel interactions in the somatosensory innervation. Our findings will shed light on the mechanisms underlying the role of extracellular vesicles in intercellular communication and of artificial lipid vesicles used as drug and vaccine vector delivery agents and adjuvants. The generated knowledge may serve to support further exploration of our hypothesis to other relevant phenomena, such as tumor-neuro-vascular interactions and the mechanisms of viral entry.