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.

Quantification of promoting efficiency and reducing toxicity of Traditional Chinese Medicine: A case study of the combination of Tripterygium wilfordii hook. f. and Lysimachia christinae hance in the treatment of lung cancer.

Traditional Chinese medicine (TCM) usually acts in the form of compound prescriptions in the treatment of complex diseases. The herbs contained in each prescription have the dual nature of efficiency and toxicity due to their complex chemical component, and the principle of prescription is usually to increase efficiency and reduce toxicity. At present, the studies on prescriptions have mainly focused on the consideration of the material basis and possible mechanism of the action mode, but the quantitative research on the compatibility rule of increasing efficiency and reducing toxicity is still the tip of the iceberg. With the extensive application of computational pharmacology technology in the research of TCM prescriptions, it is possible to quantify the mechanism of synergism and toxicity reduction of the TCM formula. Currently, there are some classic drug pairs commonly used to treat complex diseases, such as Tripterygium wilfordii Hook. f. with Lysimachia christinae Hance for lung cancer, Aconitum carmichaelii Debeaux with Glycyrrhiza uralensis Fisch. in the treatment of coronary heart disease, but there is a lack of systematic quantitative analysis model and strategy to quantitatively study the compatibility rule and potential mechanism of synergism and toxicity reduction. To address this issue, we designed an integrated model which integrates matrix decomposition and shortest path propagation, taking into account both the crosstalk of the effective network and the propagation characteristics. With the integrated model strategy, we can quantitatively detect the possible mechanisms of synergism and attenuation of Tripterygium wilfordii Hook. f. and Lysimachia christinae Hance in the treatment of lung cancer. The results showed the compatibility of Tripterygium wilfordii Hook. f. and Lysimachia christinae Hance could increase the efficacy and decrease the toxicity of lung cancer treatment through MAPK pathway and PD-1 checkpoint pathway in lung cancer.

A hillock-like phenomenon with low friction and adhesion on a graphene surface induced by relative sliding at the interface of graphene and the SiO2 substrate using an AFM tip.

Graphene demonstrates high potential as an atomically thin solid lubricant for sliding interfaces in industry. However, graphene as a coating material does not always exhibit strong adhesion to any substrates. When the adhesion of graphene to its substrate weakens, it remains unknown whether relative sliding at the interface exists and how the tribological properties of the graphene coating changes. In this work, we first designed a method to weaken the adhesion between graphene and its SiO2 substrate. Then the graphene with weakened adhesion to its substrate was rubbed using an AFM tip, where we found a novel phenomenon: the monolayer graphene not only no longer protected the SiO2 substrate from deformation and damage, but also prompted the formation of hillock-like structures with heights of approximately tens of nanometers. Moreover, the surface of the hillock-like structure exhibited very low adhesion and a continuously decreasing friction force versus sliding time. Comparing the hillock-like structure on the bare SiO2 surface and the proposed force model, we demonstrated that the emergence of the hillock-like structure (with very low adhesion and continuously decreasing friction) was ascribed to the relative sliding at the graphene/substrate interface caused by the mechanical shear of the AFM tip. Our findings reveal a potential failure of the graphene coating when the adhesion strength between graphene and its substrate is damaged or weakened and provide a possibility for in situ fabrication of a low friction and adhesion micro/nanostructure on a SiO2/graphene surface.