Mechanosensitive ion channel inhibitors promote the stiffening of the plasma membrane of mouse sensory neurons

Soft Matter. 2019 Oct 23;15(41):8320-8328. doi: 10.1039/c9sm01230c.

Abstract

The mechanosensitivity of cells depends on the lipid-protein interactions of the plasma membrane. Affectations in the lipid region of the plasma membrane affect the transduction of mechanical forces, and any molecule that modifies the biophysical integrity of the lipid bilayer can alter the mechanical activity of the proteins inside the membrane. To understand whether inhibitors of mechanically activated ion channels affect the mechanical properties of the plasma membrane, we evaluated the rigidity of the membrane of sensory neurons of the DRG of mice using a variant of the scanning ion conductance microscopy method, which allows us to calculate the Young's modulus of individual cells before and after the perfusion of different doses of Gd3+, ruthenium red and GsMTx-4. Our results suggest that these molecules compromise the membrane by increasing the Young's modulus value, which indicates that the membrane becomes more rigid; these compounds act through different mechanisms and by a non-specific manner, each one shows a certain preference for specific cell subpopulations, depending on their cell size and their reactivity to isolectin B4. Our results support the idea that the biophysical properties that result from the interactions that arise in the membranes are part of the mechanotransduction process.

MeSH terms

  • Animals
  • Cadmium / metabolism
  • Cell Line
  • Cell Membrane / metabolism*
  • Cells, Cultured
  • Elastic Modulus
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Male
  • Mechanotransduction, Cellular
  • Membrane Transport Modulators / metabolism*
  • Mice
  • Ruthenium Red / metabolism
  • Sensory Receptor Cells / metabolism*
  • Sensory Receptor Cells / ultrastructure*
  • Signal Transduction
  • Spider Venoms / metabolism

Substances

  • Intercellular Signaling Peptides and Proteins
  • MTx4 protein, Grammostola spatulata
  • Membrane Transport Modulators
  • Spider Venoms
  • Cadmium
  • Ruthenium Red