Spatial confinement induces oscillatory migration of epidermal keratinocytes and forms a three-compartment epithelial structure with epithelial–mesenchymal transition dynamics

Spatial confinement triggers a unique oscillatory migration behavior in epidermal keratinocytes, leading to the formation of a three-compartment epithelial structure, according to a recent study. This discovery provides insight into the dynamics of wound healing and the mechanisms behind epithelial cells' transformation during migration.

Keratinocytes (KCs), the primary skin epithelial cells, were placed on a microporous membrane and observed to migrate through pores larger than 3.0 µm in diameter. The 3.0-µm-pored membrane, however, induced a remarkable three-compartment epithelial structure: a stratified epithelium above the membrane, KCs displaying epithelial-to-mesenchymal transition (EMT) within the micropores, and a new stratified epithelium beneath the membrane.

The oscillatory migration pattern of KCs, characterized by actin-rich filopodia-like structures extending into and out of the 3.0 µm micropores, was made evident through live imaging. This movement was linked to the unidirectional migration of cells into larger micropores. The findings also identified two key factors that modulate the entry and exit of KCs through the 3.0 µm micropores: Piezo1 and keratin 6. Both of these factors have negative effects on the KCs' movement within the confined space.

The study concludes that non-cancerous epithelial cells, such as KCs, exhibit an oscillatory migration behavior when confined within specific spaces. This behavior contributes to the formation of a three-compartment epithelial structure, which can be used as a model for understanding wound healing processes.