biostudies-literatureKorkmazhan ENIGMS NIH HHS1029-1037https://www.ebi.ac.uk/biostudies/studies/S-EPMC8943750biostudies-literatureUnknown121(6)Adhesion between animal cells and the underlying extracellular matrix is challenged during wounding, cell division, and a variety of pathological processes. How cells recover adhesion in the immediate aftermath of detachment from the extracellular matrix remains incompletely understood, due in part to technical limitations. Here, we used acute chemical and mechanical perturbations to examine how epithelial cells respond to partial delamination events. In both cases, we found that cells extended lamellipodia to establish readhesion within seconds of detachment. These lamellipodia were guided by sparse membrane tethers whose tips remained attached to their original points of adhesion, yielding lamellipodia that appear to be qualitatively distinct from those observed during cell migration. InBiophysical journalTether-guided lamellipodia enable rapid wound healing.PMC8943750F32 GM125113T32 GM008294R35 GM130332Kennard ASKorkmazhan EVasquez CGGarzon-Coral CDunn ARfalseTether-guided lamellipodia enable rapid wound healing.Adhesion between animal cells and the underlying extracellular matrix is challenged during wounding, cell division, and a variety of pathological processes. How cells recover adhesion in the immediate aftermath of detachment from the extracellular matrix remains incompletely understood, due in part to technical limitations. Here, we used acute chemical and mechanical perturbations to examine how epithelial cells respond to partial delamination events. In both cases, we found that cells extended lamellipodia to establish readhesion within seconds of detachment. These lamellipodia were guided by sparse membrane tethers whose tips remained attached to their original points of adhesion, yielding lamellipodia that appear to be qualitatively distinct from those observed during cell migration. In2022-01-01T00:00:00Z2022 Mar2026-06-18T08:44:12.865Z2025-04-06T18:34:07.011ZS-EPMC89437503516786310.1016/j.bpj.2022.02.006