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

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.

The nuclear piston activates mechanosensitive ion channels to generate cell migration paths in confining microenvironments

“…We show that mechanosensitive ions subsequently play a critical role in driving the osmotic pressure changes that overcome the increase in hydrostatic pressure in the protrusion to drive protrusion expansion. While we focused on TRPV4 and NHE-1, a recent study found that the mechanosensitive ion channel TRPM7 plays a central role in how cancer cells sense hydraulic pressure and cross-sectional area in microfabricated microchannels (24). This suggests that other mechanosensitive ion channels could also be involved in regulating the nuclear piston.…”

Dorsoventral polarity directs cell responses to migration track geometries

“…PDMS-based microfluidic devices, which consist of an array of parallel vertical or lateral channels with a fixed channel length of 200 μm and a constant cross-sectional area of 30 μm 2 , were fabricated as described previously ( 41 – 43 ). Vertical confinement was applied by inducing cells to migrate through a channel with a height, H , of 3 μm (and a width, W , of 10 μm), whereas in lateral confinement the width was set to 3 μm (and H = 10 μm).…”

A Procarcinogenic Colon Microbe Promotes Breast Tumorigenesis and Metastatic Progression and Concomitantly Activates Notch and β-Catenin Axes

“…To query if BFT exposure truly leads to a migratory/invasive phenotype, single cell migration was investigated using a microfluidic device where cells were allowed to migrate across microfluidic channels of different widths ranging from 3 μm to 50 μm towards a gradient of EGF used as a chemo-attractant (27,28).…”