Dietary fatty acids fine-tune Piezo1 mechanical response

Nat Commun. 2019 Mar 13;10(1):1200. 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anemia, Hemolytic, Congenital / diet therapy*
  • Anemia, Hemolytic, Congenital / genetics
  • Animals
  • Cell Membrane / metabolism
  • Cell Membrane / ultrastructure
  • Dietary Fats / administration & dosage
  • Dietary Fats / metabolism*
  • Fatty Acids / metabolism
  • Fatty Acids, Unsaturated / administration & dosage
  • Fatty Acids, Unsaturated / metabolism
  • Gain of Function Mutation
  • HEK293 Cells
  • Humans
  • Hydrops Fetalis / diet therapy*
  • Hydrops Fetalis / genetics
  • Ion Channel Gating / physiology*
  • Ion Channels / genetics
  • Ion Channels / metabolism*
  • Lipid Metabolism / physiology
  • Mice
  • Microscopy, Atomic Force
  • Patch-Clamp Techniques


  • Dietary Fats
  • Fatty Acids
  • Fatty Acids, Unsaturated
  • Ion Channels
  • PIEZO1 protein, human
  • Piezo1 protein, mouse
  • margaric acid

Supplementary concepts

  • Xerocytosis, hereditary