Dietary fatty acids fine-tune Piezo1 mechanical response

Luis O. Romero, Andrew E. Massey, Alejandro D. Mata-Daboin, Francisco J. Sierra-Valdez, Subhash C. Chauhan, Julio F. Cordero-Morales and Valeria Vásquez ()
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Luis O. Romero: University of Tennessee Health Science Center
Andrew E. Massey: University of Tennessee Health Science Center
Alejandro D. Mata-Daboin: University of Tennessee Health Science Center
Francisco J. Sierra-Valdez: University of Tennessee Health Science Center
Subhash C. Chauhan: University of Tennessee Health Science Center
Julio F. Cordero-Morales: University of Tennessee Health Science Center
Valeria Vásquez: University of Tennessee Health Science Center

Nature Communications, 2019, vol. 10, issue 1, 1-14

Abstract: Abstract 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.

Date: 2019
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DOI: 10.1038/s41467-019-09055-7

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