Navigating confinement: Mechanotransduction and metabolic adaptation

Cell migration through confined spaces is a critical process influenced by the complex three-dimensional (3D) architecture of the local microenvironment and the surrounding extracellular matrix (ECM). Cells in vivo experience diverse fluidic signals, such as extracellular fluid viscosity, hydraulic resistance, and shear forces, as well as solid cues, like ECM stiffness and viscoelasticity. These fluidic and solid stressors activate mechanotransduction processes and regulate cell migration. They also drive metabolic reprogramming, dynamically altering glycolysis and oxidative phosphorylation to meet the cell's energy demands in different microenvironments. This review discusses recent advances on the mechanisms of cell migration in confinement and how confinement-induced cellular behavior leads to metabolic reprogramming.