Temporary increase in plasma membrane tension coordinates the activation of exocytosis and contraction during cell spreading

TLDR

Cell migration and spreading require coordinated membrane trafficking, actomyosin contraction, and changes in plasma membrane tension and area, yet the underlying biophysical mechanism remains unknown. The study proposes that plasma membrane tension serves as a global physical cue to regulate cell motility. During spreading, a transient >2‑fold rise in membrane tension following lamellipodia flattening triggers exocytosis and myosin contraction, and manipulating tension confirms that membrane tension synchronizes trafficking, contraction, and area change.

Abstract

Cell migration and spreading involve the coordination of membrane trafficking, actomyosin contraction, and modifications to plasma membrane tension and area. The biochemical or biophysical basis for this coordination is however unknown. In this study, we show that during cell spreading, lamellipodia protrusion flattens plasma membrane folds and blebs and, once the plasma membrane area is depleted, there is a temporary increase in membrane tension by over twofold that is followed by activation of exocytosis and myosin contraction. Further, an artificial increase in plasma membrane tension stopped lamellipodia protrusion and activated an exocytotic burst. Subsequent decrease in tension restored spreading with activation of contraction. Conversely, blebbistatin inhibition of actomyosin contraction resulted in an even greater increase in plasma membrane tension and exocytosis activation. This spatiotemporal synchronization indicates that membrane tension is the signal that coordinates membrane trafficking, actomyosin contraction, and plasma membrane area change. We suggest that cells use plasma membrane tension as a global physical parameter to control cell motility.