Assembly of Tetraspanin-enriched macrodomains contains membrane damage to facilitate repair.

Various mechanisms contribute to membrane repair but the machinery that mediates the repair of large wounds on the plasma membrane is less clear. We found that shortly after membrane damage, Tetraspanin-enriched macrodomains are assembled around the damage site. Tetraspanin-enriched macrodomains are in the liquid-ordered phase and form a rigid ring around the damaged site. This restricts the spread of the damage and prevents membrane disintegration, thus facilitating membrane repair by other mechanisms. Functionally, Tetraspanin 4 helps cells mitigate damage caused by laser, detergent, pyroptosis and natural killer cells. We propose that assembly of Tetraspanin-enriched macrodomains creates a physical barrier to contain membrane damage.