Acute effects of cell stretch on keratin filaments in A549 lung cells. Issue 8 (6th July 2020) - Lutz, Anngrit
Abstract: Keratin filaments (KFs) comprise the intermediate filaments of epithelial cells and are well known for their cytoprotective properties and their mechanical resilience. Although, several studies have demonstrated KFs' remarkable tensile properties relatively little is known about acute implications of mechanical stretch on KFs in living cells. This includes structural effects on the KFs and their higher level assembly structures as well as posttranslational response mechanisms to possibly modify KF's properties. We subjected simple epithelial A549 lung cells to 30% unidirectional stretch and already after 10 seconds we observed morphological changes of the KF‐network as well as structural effects on their desmosomal anchor sites—both apparently caused by the tensile strain. Interestingly, the effect on the desmosomes was attenuated after 30 seconds of cell stretch with a concomitant increase in phosphorylation of keratin8‐S432, keratin18‐S53, and keratin18‐S34 without an apparent increase in keratin solubility. When mimicking the phosphorylation of keratin18‐S34 the stretch‐induced effect on the desmosomes could be diminished and probing the cell surface with atomic force microscopy showed a lowered elastic modulus. We conclude that the stretch‐induced KF phosphorylation affects KF's tensile properties, probably to lower the mechanical load on strained desmosomal cell‐cell contacts, and hence, preserve epithelial integrity.