Mechanical Behavior of A375 Cell Membrane Puncture Based on AFM Experiments and Finite Element Analysis

Cell membrane rupture plays a pivotal role in drug delivery, physical tumor therapies, and cellular mechanobiology. Despite its importance, the quantitative mechanical mechanisms governing membrane failure remain poorly understood. A375 human melanoma cells were employed as a representative model to investigate membrane rupture behavior through the integration of atomic force microscopy (AFM) puncture experiments and finite element simulations. The AFM measurements yielded a membrane rupture force of 27.09 ± 0.446 nN, an indentation depth of 3.46 ± 0.429 μm, and a rupture energy of 16.77 ± 0.902 fJ. Based on these experimentally obtained parameters, a finite element model was developed to reproduce the stress evolution and failure process associated with membrane puncture. The predicted equivalent stress, equivalent strain, and strain energy density differed from the experimentally derived values by only 4.4%, 4.9%, and 8.1%, respectively, demonstrating good agreement between simulation and experiment. Comparative analyses of linear elastic, elastoplastic, and hyperelastic constitutive formulations further revealed that the hyperelastic model provided the most accurate representation of membrane puncture behavior. This finding highlights the dominant role of large deformation nonlinear mechanics in governing membrane failure during AFM puncture. Overall, the combined experimental and computational framework established in this work offers quantitative insights into the mechanics of cell membrane rupture and provides a useful platform for future investigations of membrane damage mechanisms and biomechanical modeling of living cells.