Ultimately Adaptive Fluid Interfacial Phospholipid Membranes Unveiled Unanticipated High Cellular Mechanical Work

Abstract Living cells actively interact biochemically and mechanically with the surrounding extracellular matrices (ECMs) and undergo dramatic morphological and dimensional transitions, concomitantly remodeling ECMs. However, there is no suitable method to quantitatively discuss the contribution of mechanical interactions in such mutually adaptive processes. Herein, a highly deformable “living” cellular scaffold is developed to evaluate overall mechanical energy transfer between cell and ECMs. It is based on the water–perfluorocarbon interface decorated with phospholipids bearing a cell‐adhesive ligand and fluorescent tag. The bioinert nature of the phospholipid membranes prevents the formation of solid‐like protein nanofilms at the fluid interface, enabling to visualize and quantify cellular mechanical work against the ultimately adaptive model ECM. A new cellular wetting regime is identified, wherein interface deformation proceeds to cell flattening, followed by its eventual restoration. The cellular mechanical work during this adaptive wetting process is one order of magnitude higher than those reported with conventional elastic platforms. The behavior of viscous liquid drops at the air–water interface can simulate cellular adaptive wetting, suggesting that overall viscoelasticity of the cell body predominates the emergent wetting regime and regulates mechanical output. Cellular‐force‐driven high‐energy states on the adaptive platform can be useful for cell fate manipulation.