biostudies-literatureScholz JEuropean Research CouncilWellcome Trusteadp5929https://www.ebi.ac.uk/biostudies/studies/S-EPMC11524191biostudies-literatureUnknown10(44)Cortical formins, pivotal for the assembly of linear actin filaments beneath the membrane, exert only minor effects on unconfined cell migration of weakly and moderately adherent cells. However, their impact on migration and mechanostability of highly adherent cells remains poorly understood. Here, we demonstrate that loss of cortical actin filaments generated by the formins mDia1 and mDia3 drastically compromises cell migration and mechanics in highly adherent fibroblasts. Biophysical analysis of the mechanical properties of the mutant cells revealed a markedly softened cell cortex in the poorly adherent state. Unexpectedly, in the highly adherent state, associated with a hyperstretched morphology with exaggerated focal adhesions and prominent high-strain stress fibers, they exhibited eveScience advancesDecisive role of mDia-family formins in cell cortex function of highly adherent cells.PMC11524191223125/Z/21/Z835102Merkel RLange FHersch NPeckham MPich ALitschko CSpringer RJakobs SKaufmann TStephan TBruhmann SFaix JMijanovic LCsiszar APerez AGFischer LSTarantola MKorber SGrashoff CScholz JfalseDecisive role of mDia-family formins in cell cortex function of highly adherent cells.Cortical formins, pivotal for the assembly of linear actin filaments beneath the membrane, exert only minor effects on unconfined cell migration of weakly and moderately adherent cells. However, their impact on migration and mechanostability of highly adherent cells remains poorly understood. Here, we demonstrate that loss of cortical actin filaments generated by the formins mDia1 and mDia3 drastically compromises cell migration and mechanics in highly adherent fibroblasts. Biophysical analysis of the mechanical properties of the mutant cells revealed a markedly softened cell cortex in the poorly adherent state. Unexpectedly, in the highly adherent state, associated with a hyperstretched morphology with exaggerated focal adhesions and prominent high-strain stress fibers, they exhibited eve2024-01-01T00:00:00Z2024 Nov2026-07-16T03:08:34.112Z2025-04-04T02:34:21.683ZS-EPMC115241913947561010.1126/sciadv.adp5929