biostudies-literatureLolo FNEuropean Research Council120-133https://www.ebi.ac.uk/biostudies/studies/S-EPMC9859760biostudies-literatureUnknown25(1)In 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 mechanoproteNature cell biologyCaveolin-1 dolines form a distinct and rapid caveolae-independent mechanoadaptation system.PMC9859760883739Pavon DMArroyo MSeemann EEscolano JCMartinez de Benito FWalani NCaiolfa VRLamaze CSanchez SANavajas DZalvidea DJimenez-Carretero DEcharri AQualmann BGuck JLolo FNRoca-Cusachs PCojoc GViaris de Lesegno CTrepat XDel Pozo MAKessels MMSanchez-Alvarez MZamai MUriarte JJfalseCaveolin-1 dolines form a distinct and rapid caveolae-independent mechanoadaptation system.In 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 mechanoprote2023-01-01T00:00:00Z2023 Jan2026-05-29T02:22:19.232Z2025-02-19T02:24:01.445ZS-EPMC98597603654398110.1038/s41556-022-01034-3