Dietary fatty acids fine-tune Piezo1 mechanical response

• Published in: Nature communications Vol. 10; no. 1; p. 1200
• Main Authors: Romero, Luis O, Massey, Andrew E, Mata-Daboin, Alejandro D, Sierra-Valdez, Francisco J, Chauhan, Subhash C, Cordero-Morales, Julio F, Vásquez, Valeria
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 13.03.2019; Nature Publishing Group UK; Nature Portfolio
• Subjects: Anemia, Hemolytic, Congenital - diet therapy; Anemia, Hemolytic, Congenital - genetics; Animals; Cell adhesion & migration; Cell Membrane - metabolism; Cell Membrane - ultrastructure; Cell migration; Dairy products; Deactivation; Dehydration; Diet; Dietary Fats - administration & dosage; Dietary Fats - metabolism; Dietary supplements; Erythrocytes; Fatty acids; Fatty Acids - metabolism; Fatty Acids, Unsaturated - administration & dosage; Fatty Acids, Unsaturated - metabolism; Fish oils; Force measurement; Gain of Function Mutation; HEK293 Cells; Humans; Hydrops Fetalis - diet therapy; Hydrops Fetalis - genetics; Inactivation; Ion Channel Gating - physiology; Ion channels; Ion Channels - genetics; Ion Channels - metabolism; Lipid Metabolism - physiology; Lipids; Mechanical analysis; Membrane composition; Metabolism; Mice; Microscopy, Atomic Force; Mutation; Patch-Clamp Techniques; Phenotypes; Polyunsaturated fatty acids; Signal processing; Signal transduction; Stiffness
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-019-09055-7

Mechanosensitive ion channels rely on membrane composition to transduce physical stimuli into electrical signals. The Piezo1 channel mediates mechanoelectrical transduction and regulates crucial physiological processes, including vascular architecture and remodeling, cell migration, and erythrocyte volume. The identity of the membrane components that modulate Piezo1 function remain largely unknown. Using lipid profiling analyses, we here identify dietary fatty acids that tune Piezo1 mechanical response. We find that margaric acid, a saturated fatty acid present in dairy products and fish, inhibits Piezo1 activation and polyunsaturated fatty acids (PUFAs), present in fish oils, modulate channel inactivation. Force measurements reveal that margaric acid increases membrane bending stiffness, whereas PUFAs decrease it. We use fatty acid supplementation to abrogate the phenotype of gain-of-function Piezo1 mutations causing human dehydrated hereditary stomatocytosis. Beyond Piezo1, our findings demonstrate that cell-intrinsic lipid profile and changes in the fatty acid metabolism can dictate the cell's response to mechanical cues.