The Insertion Mechanism of a Living Cell Determined by the Stress Segmentation Effect of the Cell Membrane during the Tip-Cell Interaction

Atomic force microscopy probes are proved to be powerful tools to measure and manipulate the individual cell, providing potential applications for the controlled drug/protein delivery. However, the measured insertion efficiency varies dramatically from 20 to 80%, in some cases, the nanotip can never penetrate the cell membrane no matter how much force is applied to it. Thus, the insertion mechanism of a living cell during the tip-cell interaction must be thoroughly investigated before this technology comes into practical applications. In this work, a multistructural cell model is established to study the tip-membrane interaction. The simulation results show that the stress of the cell membrane can be divided into two stages by the stress segmentation point S. After point S, the stress of the cell membrane increases slightly and most of the indentation force is allocated to the cytoskeleton. This phenomenon is called stress segmentation effect of the cell membrane, which confirms the hypothesis based on the experimental studies. Moreover, according to the experimental and numerical studies, the hypothesis of the stress segmentation effect also explains the reason that modifying the cell membrane or using the manmade sharpened nanotip can increase the insertion efficiency.