Ge(001) before and after gold evaporation and annealing
Kernel of the 4-probe microscope (left), crushed tip on Si surface (middle), two STM tips over gold structures on Ge(001) surface

The influence of drugs on the phenotype of the cells

Effect of pyridinium salts on the elasticity of the endothelial cells

Civilization diseases, like arteriosclerosis and diabetics are a strong motivation for the search of prospective endothelium targeted drugs. Presented work comprises the study on the influence of three prospective endothelial agents - pyridinium salts::1-Methylnicotinamide (MNA), 1 ,4-dimethylpyridinium chloride (1,4-DMP), 1- methylpyridinium chloride (1-MP) on the changes in elasticity and NO production of the endothelial cells. The cells were incubated in medium solution, and stimulated with examined agents for different incubation periods (1h, 3h, 6h, 12h and 24h). The effect of pyridinium salt was investigated for selected concentrations: MNA (10µM, 100nM); 1.4-DMP (20nM, 100 nM) and 1-MP (1µM, 100nM). Nanoindentation spectroscopy with an AFM tip, F-actin fluorescent staining and the measurement of NO production were used to characterize the changes in the endothelial cell phenotype influenced by the endothelial agents. The changes in elasticity parameter E (reduced Young’s modulus) are examined in relation to the stimulation period. The acquired data are compared with the results obtained at control conditions. The elasticity parameter changes of the cells after activation of the tested compounds are visible for longer incubation times, i.e. more than 6h. Incubation of cells with a concentration of 100nM for MNA gives approximate values ​of the elasticity parameter as the reference, while for higher concentrations - 10µM increased elasticity parameter for longer periods is observed. Cells behave similarly incubated with 1.4-DMP i.e. for both the concentration 20nM and 100nM stiffness increases at longer exposures. However, quite the opposite effect can be seen in case of 1-MP, followed by softening of the cells with increasing time of incubation, and this observation complements with the results of NO production by the cells. There is a hypothesis that longer exposure time, e.g. 12h, can be a unique model for studying the interaction of the pyridinium salt on the endothelial cells.

Elasticity changes anti-correlate with NO production for human endothelial cells stimulated with TNF-α

Tumor necrosis factor alpha (TNF-α)is a critical cytokine that is involved in systemic inflammatory response and contributes to the activation of the pro- inflammatory phenotype of the endothelium. In the present study, effects of TNF-α on morphology and elasticity of endothelium in relation to the production of NO and actin fiber reorganization were analyzed in human dermal microvascular endothelial cells. The cells were incubated in MCDB medium solution and stimulated with 10 ng/ml of TNF-α. Atomic force microscopy measurements have enabled characterization of cell morphology and elastic properties in physiological conditions. The spectrophotometric Griess method was applied to estimate nitric oxide (NO) production of the cells. We demonstrated that TNF-α-induced changes in elasticity of endothelium anti-correlate with NO production and are associated with the reorganization of actin cytoskeleton.

Szczygiel, A. M., Brzezinka, G., Targosz-Korecka, M., Chlopicki, S., & Szymonski, M. (2011). Elasticity changes anti-correlate with NO production for human endothelial cells stimulated with TNF-α. Pflügers Archiv - European Journal of Physiology, 463(3), 487–496. doi:10.1007/s00424-011-1051-1

Effect of selected drugs used in asthma treatment on morphology and elastic properties of red blood cells

The main function of red blood cells is to transport oxygen to all parts of the body with the help of hemoglobin. Other proteins of the cell membrane can attach xenobiotics (eg, drugs) from the blood and transport them throughout the body. Only drugs able to bind to the membrane of the red blood cell can modify its structure and elastic properties. The morphology and local elastic properties of living red blood cells incubated with drug solutions commonly used in the treatment of severe asthma were studied by atomic force microscopy and nanoindentation with an atomic force microscopy tip. The elasticity modules of native red blood cells, as well as those incubated with two types of drugs, ie, aminophylline and methylprednisolone, were determined from experimentally measured nanoindentation curves. The elasticity modules of erythrocytes incubated with aminophylline were substantially higher than those obtained for nonincubated native, ie, healthy, red blood cells. The increase of the elasticity module obtained for aminophylline can reduce the cell’s ability to bind oxygen and transport it through capillaries.

Zuk, A., Targosz-Korecka, M., & Szymonski, M. (2011). Effect of selected drugs used in asthma treatment on morphology and elastic properties of red blood cells. International journal of nanomedicine, 6, 249–57. doi:10.2147/IJN.S15802

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