Abstract
Despite the importance in various cellular processes, the nanomechanical responses of the living cell membrane have been elusive due to complexities in the membrane associated with the hidden architecture of multiple molecular components, including the lipid bilayer. Here, combined experimental and theoretical frameworks that can probe and interpret nanomechanical responses of the cell membrane are demonstrated. A magnetic tweezer assay was introduced to apply pico-Newton scale forces to lipids and E-cadherin molecules at the living cell surface. Two unique classes of force-extension curves were identified: one with a deflection transition (Type I) and another with a discontinuous transition (Type II). The repeated observations of these responses, regardless of cell type and targeted cell surface molecule, suggest the Type I and II curves are the primary nanomechanical responses of cell membranes. To reproduce these responses in vitro, a model system using synthetic lipid vesicles was also developed. Together with a finite element model of lipid bilayers, the reproduced responses suggest that the confined fluidity and curvature constraints imposed on the lipid bilayer components of the cell membrane are the main parameters responsible for the generation of these responses. This work provides an insight into how forces on membrane molecules propagate to the lipid bilayer components to generate specific nanomechanical responses. In addition, the consistent results obtained using different methodologies demonstrate that the presented force-probing assays and the theoretical model can serve a combined testbed to investigate nanoscale mechanics of the living cell membrane.