Spontaneous Rotations in Epithelia as an Interplay Between Cell Polarity and Boundaries

Coordinated cellular movements are critical for morphogenesis.  However, the mechanisms that regulate the directional flow of cells are not fully understood.  Recently, Vecchio et al. investigated how spontaneous rotations are impacted by several cellular forces.   They first utilized micro-contact printing technology to create a fibronectin ring substrate that cells would adhere to to create cellular ring structures.  This allowed them to determine the optimal ring size needed for directional cellular migration. These studies revealed that a cellular ring size of 80 mm spontaneously produced cellular rotation 83% of the time.  They next sought to define the mechanisms driving cell coherence.  Using cells with labeled lamellipodia, the group found a bimodal distribution of cell polarities that created a “tug-of-war” effect critical for determining the time needed to enter coherence. When lamellipodia formation was inhibited, the tug-of-war effect was suppressed, which prevented coherence.  The group further examined the importance of cell polarity towards coherence by studying cell divisions within the ring and revealed that the opposing polarities that form in dividing cells significantly impacted coherence.   They also investigated why these ring structures were maintained, as no physical barriers kept the cells in place.  They used laser ablation studies to determine that acto-myosin cables were integral in imposing tangential polarity.  Cells expressing caldesmon, which ultimately inhibits myosin ATPase activity, showed decreased cable contractility and extended out of the rings with radial motion.  Additional studies were performed to show that the forces active at the boundaries were RhoA dependent.  Cytoskeleton Inc.’s rhodamine fibronectin (Cat. # FNR01) was a critical reagent used to develop the micro-contact fibronectin ring substrates, which was critical for revealing these cellular characteristics in the absence of mechanically confined boundaries.