Effect of Trastuzumab on the thermodynamic behavior and roughness of fluid membrane using unsaturated phospholipid/cholesterol mixed monolayer model.

The microenvironment near the receptor on biological membrane plays an important role in regulating drug-receptor interaction, and the interaction between drugs and lipids on membrane can also affect the microenvironment of membrane, which may affect drugs' efficacy or cause the drug resistance. Trastuzumab (Tmab) is a monoclonal antibody, used to treat early breast cancer associated with the overexpression of Human Epidermal growth factor Receptor 2 (HER2). But its effectiveness is limited due to its tendency to make tumor cells resistant to the drug. In this work, the monolayer mixed by unsaturated phospholipids (DOPC, DOPE and DOPS) and cholesterol were used as a model to simulate the fluid membrane region on biological membrane. The phospholipid/cholesterol mixed monolayers in molar ratio 7:3 and 1:1, were respectively used to simulate the one layer of simplified normal cell membrane and tumor cell membrane. The influence of this drug on the phase behavior, elastic modulus, intermolecular force, relaxation and the surface roughness of the unsaturated phospholipid/cholesterol monolayer was investigated. The results show that at 30 mN/m the increase or decrease of the elastic modulus and surface roughness of the mixed monolayer caused by Tamb depends on the type of phospholipid, but the intensity of the effect depends on the content of cholesterol, and the intensity of influence is more significant at the presence of 50% cholesterol. However, the effect of Tmab on the ordering of the DOPC/cholesterol or DOPS/cholesterol mixed monolayer is stronger when the content of cholesterol is 30%, but it was stronger for the DOPE/cholesterol mixed monolayer when the content of cholesterol is 50%. This study is helpful to understand the effects of anticancer drugs on microenvironment of cell membrane, and it has a certain reference value for the design of drug delivery system and drug target identification.