Figure 4.

Schematic of the cellular response to membrane stress failure. Calcium enters the cell through a plasma membrane defect. Sustained large elevations in intracellular Ca²⁺ produce necrosis. Smaller transients in intracellular Ca²⁺ initiate cell repair responses. Cells repair membrane defects but several mechanisms (right-hand side). Mechanism 1 involves lateral flow plasma membrane lipids driven the free energy (analogous to surface tension) at the wound edge. This mechanisms is thought to play a role in the healing of small defects. Mechanism 2 is the fusion of early endosomes with the plasma membrane. Mechanism 3 involves the coalescence of vesicular organelles (usually lysosomes), which form a patch and plugs the wound by Ca²⁺-induced, site-directed exocytosis. Wounding and repair trigger also the translocation of nuclear transcription factors like NFκ-B, leading to the induction of early stress response genes and thereby initiate proinflammatory signaling cascades.