Cell sensing and decision-making in confinement: The role of TRPM7 in a tug of war between hydraulic pressure and cross-sectional area

Sci Adv. 2019 Jul 24;5(7):eaaw7243. doi: 10.1126/sciadv.aaw7243. eCollection 2019 Jul.

Abstract

How cells sense hydraulic pressure and make directional choices in confinement remains elusive. Using trifurcating Ψ-like microchannels of different hydraulic resistances and cross-sectional areas, we discovered that the TRPM7 ion channel is the critical mechanosensor, which directs decision-making of blebbing cells toward channels of lower hydraulic resistance irrespective of their cross-sectional areas. Hydraulic pressure-mediated TRPM7 activation triggers calcium influx and supports a thicker cortical actin meshwork containing an elevated density of myosin-IIA. Cortical actomyosin shields cells against external forces and preferentially directs cell entrance in low resistance channels. Inhibition of TRPM7 function or actomyosin contractility renders cells unable to sense different resistances and alters the decision-making pattern to cross-sectional area-based partition. Cell distribution in microchannels is captured by a mathematical model based on the maximum entropy principle using cortical actin as a key variable. This study demonstrates the unique role of TRPM7 in controlling decision-making and navigating migration in complex microenvironments.

Publication types

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

MeSH terms

  • Actomyosin / metabolism
  • Calcium / metabolism
  • Cell Line, Tumor
  • Cell Surface Extensions / metabolism
  • Entropy
  • HEK293 Cells
  • Humans
  • Hydrostatic Pressure*
  • Ion Channel Gating
  • Mechanotransduction, Cellular*
  • Protein Serine-Threonine Kinases / metabolism*
  • TRPM Cation Channels / metabolism*
  • Water / chemistry*

Substances

  • TRPM Cation Channels
  • Water
  • Actomyosin
  • Protein Serine-Threonine Kinases
  • TRPM7 protein, human
  • Calcium