Lolo, Fidel-NicolásWalani, NikhilSeemann, EricZalvidea, DobrynaPavón, Dácil MaríaCojoc, GheorgheZamai, MorenoViaris de Lesegno, ChristineMartínez de Benito, FernandoSánchez-Álvarez, MiguelUriarte, Juan JoséEcharri, AsierJiménez-Carretero, DanielEscolano, Joan-CarlesSánchez, Susana ACaiolfa, Valeria RNavajas, DanielTrepat, XavierGuck, JochenLamaze, ChristopheRoca-Cusachs, PereKessels, Michael MQualmann, BrittaArroyo, Marinodel Pozo, Miguel Angel2022-12-222022-12-222022-12-21Nat Cell Biol. 2022 Dec 21http://hdl.handle.net/20.500.12105/15398In response to different types and intensities of mechanical force, cells modulate their physical properties and adapt their plasma membrane (PM). Caveolae are PM nano-invaginations that contribute to mechanoadaptation, buffering tension changes. However, whether core caveolar proteins contribute to PM tension accommodation independently from the caveolar assembly is unknown. Here we provide experimental and computational evidence supporting that caveolin-1 confers deformability and mechanoprotection independently from caveolae, through modulation of PM curvature. Freeze-fracture electron microscopy reveals that caveolin-1 stabilizes non-caveolar invaginations-dolines-capable of responding to low-medium mechanical forces, impacting downstream mechanotransduction and conferring mechanoprotection to cells devoid of caveolae. Upon cavin-1/PTRF binding, doline size is restricted and membrane buffering is limited to relatively high forces, capable of flattening caveolae. Thus, caveolae and dolines constitute two distinct albeit complementary components of a buffering system that allows cells to adapt efficiently to a broad range of mechanical stimuli.engVoRhttp://creativecommons.org/licenses/by/4.0/Atribución 4.0 Internacional3654398110.1038/s41556-022-01034-31476-4679Nature cell biologyopen access