Hydraulic resistance induces cell phenotypic transition in confinement

Area of Science:

• Cell biology
• Biophysics
• Mechanobiology

Background:

• Cells in confined environments undergo mesenchymal-to-amoeboid transitions.
• Microenvironment topography influences cellular hydraulic resistance.
• Cellular responses to hydraulic resistance remain largely unexplored.

Purpose of the Study:

• Investigate how cells respond to varying hydraulic resistance.
• Characterize the phenotypic transitions cells undergo under confinement.
• Elucidate the mechanisms controlling cell phenotype in response to physical cues.

Main Methods:

• Automated morphological tracking and wavelet analysis.
• Fluorescence recovery after photobleaching (FRAP) for actin dynamics.
• TRPM7 mechanosensor inhibition.
• Mathematical modeling of cellular processes.

Main Results:

• Cell phenotype shifts from amoeboid to mesenchymal with increasing hydraulic resistance.
• Phenotypic transition exhibits oscillatory behavior: blebbing to actin network formation and back.
• Elevated resistance accelerates amoeboid-to-mesenchymal transition by promoting focal adhesion maturation and long actin filaments.
• TRPM7 inhibition renders the transition period independent of resistance.
• Mathematical models link calcium oscillations, actomyosin dynamics, and force generation.

Conclusions:

• Hydraulic resistance is a critical physical cue regulating cell phenotype.
• Oscillatory phenotypic transitions are driven by intracellular calcium and actomyosin dynamics.
• TRPM7 acts as a key mechanosensor in this process.
• Developed a method to correlate fluorescent signal fluctuations with morphological oscillations.