TY - JOUR
T1 - Cell sensing and decision-making in confinement
T2 - The role of TRPM7 in a tug of war between hydraulic pressure and cross-sectional area
AU - Zhao, Runchen
AU - Afthinos, Alexandros
AU - Zhu, Tian
AU - Mistriotis, Panagiotis
AU - Li, Yizeng
AU - Serra, Selma A.
AU - Zhang, Yuqi
AU - Yankaskas, Christopher L.
AU - He, Shuyu
AU - Valverde, Miguel A.
AU - Sun, Sean X.
AU - Konstantopoulos, Konstantinos
N1 - Publisher Copyright:
Copyright © 2019 The Authors,
PY - 2019/7/24
Y1 - 2019/7/24
N2 - How cells sense hydraulic pressure and make directional choices in confinement remains elusive. Using trifurcating Y-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.
AB - How cells sense hydraulic pressure and make directional choices in confinement remains elusive. Using trifurcating Y-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.
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U2 - 10.1126/sciadv.aaw7243
DO - 10.1126/sciadv.aaw7243
M3 - Article
C2 - 31355337
AN - SCOPUS:85069920036
SN - 2375-2548
VL - 5
JO - Science Advances
JF - Science Advances
IS - 7
M1 - eaaw7243
ER -