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

Runchen Zhao | Alexandros Afthinos | Tian Zhu | Panagiotis Mistriotis | Yizeng Li | Selma A Serra | Yuqi Zhang | Christopher L Yankaskas | Shuyu He | Miguel A Valverde | Sean X Sun | Konstantinos Konstantopoulos
Science advances | 2019

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.

Pubmed ID: 31355337

Associated grants

  • Agency: NCI NIH HHS, United States
    Id: U54 CA210173
  • Agency: NCI NIH HHS, United States
    Id: T32 CA130840
  • Agency: NIGMS NIH HHS, United States
    Id: R01 GM114675
  • Agency: NCI NIH HHS, United States
    Id: T32 CA153952
  • Agency: NCI NIH HHS, United States
    Id: R01 CA183804
  • Agency: NIGMS NIH HHS, United States
    Id: R01 GM134542

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