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Nat Commun. 2019 Mar 13;10(1):1200. doi: 10.1038/s41467-019-09055-7.

Dietary fatty acids fine-tune Piezo1 mechanical response.

Author information

1
Department of Physiology, College of Medicine, University of Tennessee Health Science Center, 71S. Manassas St., Memphis, TN, 38163, USA.
2
Department of Pharmaceutical Sciences and Institute of Biomarker and Molecular Therapeutics (IBMT), College of Pharmacy, University of Tennessee Health Science Center, 881 Madison Ave., Memphis, TN, 38163, USA.
3
Centro de Investigación Biomédica, Hospital Zambrano Hellion, TecSalud, Ave. Batallon de San Patricio 112, 66278, San Pedro Garza García, Nuevo León, Mexico.
4
Tecnólogico de Monterrey, Escuela de Ingeniería y Ciencias, Ave. Eugenio Garza Sada 2501 Sur, 64849, Monterrey, Nuevo León, Mexico.
5
Department of Physiology, College of Medicine, University of Tennessee Health Science Center, 71S. Manassas St., Memphis, TN, 38163, USA. vvasquez@uthsc.edu.

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.

PMID:
30867417
PMCID:
PMC6416271
DOI:
10.1038/s41467-019-09055-7
[Indexed for MEDLINE]
Free PMC Article

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