Differential interactions of bacterial lipopolysaccharides with lipid membranes: implications for TRPA1-mediated chemosensation

Abstract

Bacterial lipopolysaccharides (LPS) activate the TRPA1 cation channels in sensory neurons, leading to acute pain and inflammation in mice and to aversive behaviors in fruit flies. However, the precise mechanisms underlying this effect remain elusive. Here we assessed the hypothesis that TRPA1 is activated by mechanical perturbations induced upon LPS insertion in the plasma membrane. We asked whether the effects of different LPS on TRPA1 relate to their ability to induce mechanical alterations in artificial and cellular membranes. We found that LPS from E. coli, but not from S. minnesota, activates TRPA1. We then assessed the effects of these LPS on lipid membranes using dyes whose fluorescence properties change upon alteration of the local lipid environment. E. coli LPS was more effective than S. minnesota LPS in shifting Laurdan’s emission spectrum towards lower wavelengths, increasing the fluorescence anisotropy of diphenylhexatriene and reducing the fluorescence intensity of merocyanine 540. These data indicate that E. coli LPS induces stronger changes in the local lipid environment than S. minnesota LPS, paralleling its distinct ability to activate TRPA1. Our findings indicate that LPS activate TRPA1 by producing mechanical perturbations in the plasma membrane and suggest that TRPA1-mediated chemosensation may result from primary mechanosensory mechanisms.

Recent Advances in Lipopolysaccharide Recognition Systems

“…Furthermore, LPS treatment-induced TRPA1 currents in isolated membrane patches suggest a role for TRPA1 in sensing membrane perturbations [12]. These observations have been strengthened by a recent study demonstrating that LPS is able to be inserted into the cell membrane of TRPA1-expressing CHO cells [84]. Importantly, when LPS was added to lipid vesicles made from 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), decreased permeability of the vesicles was noted as measured by the fluorescent probe Laurdan (6-lauroyl,1-2-dimethylamino naphthalene) with an emission shift from a 400-525 nm wavelength.…”

TRP Channels as Sensors of Chemically-Induced Changes in Cell Membrane Mechanical Properties

“…For instance, depletion of cholesterol reduces the activity of TRPV1 [85,88,89,90], TRPV4 [91] and dTRPL [92], but increases stimulation of TRPM8 [87] and TRPM3 [93]. Moreover, there is increasing evidence that TRPA1 activation maybe induced by changes in the lipid environment [94,95,96].…”

Complex Regulatory Role of the TRPA1 Receptor in Acute and Chronic Airway Inflammation Mouse Models

“…The role of TRPA1 as an LPS sensor is suggested to be evolutionarily conserved [75], that occurs via mechanical modifications of the plasma lipid membrane. Interestingly, Escherichia coli (E. coli) LPS seems to be more effective on TRPA1 than other types of endotoxins [76]. Although previous studies demonstrate TRPA1 activation by LPS and its implication in acute LPS-induced pain and neurogenic inflammation [5], the relative importance of TLR4 and TRPA1 activation by LPS in our pneumonitis model remains to be elucidated.…”