Impact of Interfacial Viscosity on the Robustness of Phospholipid‐Decorated Fluid Cell Scaffolds

The mechanical properties of the cellular microenvironment contribute significantly to cell behavior. Thus, deformable phospholipid‐decorated perfluorocarbon interfaces have emerged for further expansion of material mechanics to an ultimate soft range as cell scaffolds. In addition, a highly deformable state requires the material to be robust enough to adapt to dynamic cellular forces. However, the effect of interfacial viscosity on the cell adhesion behavior and material robustness remains unknown on the super‐soft substrate. To address these issues, an interfacial phospholipid membrane (IPLM) with tunable viscosity is constructed by varying the mixing ratio of saturated and unsaturated lipid layers. By co‐assembling a cell adhesive and fluorescent lipid into the IPLM, it is shown that higher viscosity interfaces with lower unsaturated lipid content are preferred from the viewpoint of cell spreading. However, a viscosity that is too high for 0% unsaturated lipid alters the lipid layer to a brittle solid‐like nature, making it less adaptive to cell traction‐induced high deformation. Therefore, at least a trace amount of unsaturated lipids is required to maintain the robustness of fluid scaffolds. These findings are useful for the design of biomimetic materials and the long‐term investigation of cell‐matrix mechanical interactions in highly adaptive environments.