Omega 6 Polyunsaturated Fatty Acid-Containing Phospholipids Enhance Neuronal Cell Mechanics and Touch in C. Elegans

Abstract

Mechano-electrical transduction (MeT) channels embedded in neuronal cell membranes are essential for touch and proprioception. Little is understood about the interplay between native MeT channels and membrane phospholipids, in part because few techniques are available for altering plasma membrane composition in vivo. Here, we leverage genetic dissection, chemical complementation, and optogenetics to establish that arachidonic acid (AA), an omega 6 polyunsaturated fatty acid (PUFA), enhances touch sensation and mechanoelectrical transduction activity while incorporated into membrane phospholipids in C. elegans touch receptor neurons (TRNs). We found that arachidonic acid acts cell autonomously, since we show that enzymes needed for its synthesis are expressed in TRNs. We also established that the membrane viscoelastic properties of TRNs lacking omega 6 PUFAs are altered (i.e., membrane bending and viscosity), yielding less flexible membranes than wild type, as determined by atomic force microscopy (AFM) based single-tether extrusion. Our data suggest that the defect in touch sensation likely reflects a loss of mechanotransduction rather than lack of excitability or downstream signaling. These findings establish that polyunsaturated phospholipids are crucial determinants of both the biochemistry and mechanics of mechanoreceptor neurons and reinforce the idea that sensory mechanotransduction in animals relies on a cellular machine composed of both proteins and membrane lipids.