Role of membrane-tension gated Ca2+ flux in cell mechanosensation

J Cell Sci. 2018 Feb 22;131(4):jcs208470. doi: 10.1242/jcs.208470.

Abstract

Eukaryotic cells are sensitive to mechanical forces they experience from the environment. The process of mechanosensation is complex, and involves elements such as the cytoskeleton and active contraction from myosin motors. Ultimately, mechanosensation is connected to changes in gene expression in the cell, known as mechanotransduction. While the involvement of the cytoskeleton in mechanosensation is known, the processes upstream of cytoskeletal changes are unclear. In this paper, by using a microfluidic device that mechanically compresses live cells, we demonstrate that Ca2+ currents and membrane tension-sensitive ion channels directly signal to the Rho GTPase and myosin contraction. In response to membrane tension changes, cells actively regulate cortical myosin contraction to balance external forces. The process is captured by a mechanochemical model where membrane tension, myosin contraction and the osmotic pressure difference between the cytoplasm and extracellular environment are connected by mechanical force balance. Finally, to complete the picture of mechanotransduction, we find that the tension-sensitive transcription factor YAP family of proteins translocate from the nucleus to the cytoplasm in response to mechanical compression.

Keywords: Ca2+ channels; Cell cortex; Mechanosensation; Tension-activated channel.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Calcium Signaling / genetics
  • Cell Cycle Proteins
  • Cell Line
  • Cell Membrane / chemistry
  • Cell Membrane / genetics
  • Cytoplasm / chemistry
  • Cytoplasm / genetics
  • Cytoskeleton / chemistry*
  • Cytoskeleton / genetics
  • Humans
  • Lab-On-A-Chip Devices
  • Mechanical Phenomena*
  • Mechanotransduction, Cellular / genetics*
  • Muscle Contraction / genetics
  • Myosins / chemistry*
  • Myosins / genetics
  • Nuclear Proteins / chemistry
  • Nuclear Proteins / genetics
  • Osmotic Pressure
  • Transcription Factors / chemistry
  • Transcription Factors / genetics
  • rho GTP-Binding Proteins / chemistry
  • rho GTP-Binding Proteins / genetics

Substances

  • Cell Cycle Proteins
  • Nuclear Proteins
  • Transcription Factors
  • YY1AP1 protein, human
  • Myosins
  • rho GTP-Binding Proteins