Various mechanisms contribute to membrane repair1-8 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.
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