Biomedical subjects

Tilen Koklic

Publications and source records attributed to Tilen Koklic.

4 recordsLinked to original sources

PubMed2006

Increase in fluidity in the membrane of MT3 breast cancer cells correlates with enhanced cell adhesion in vitro and increased lung metastasis in NOD/SCID mice.

To study whether membrane fluidity of tumor cells have an influence on metastasis, MT3 breast cancer cells harvested during exponential growth and under confluent conditions were compared. Electron paramagnetic resonance (EPR) data revealed that, in comparison to growing cells, confluent cells have a significant higher fluidity in their membrane related to a higher relative portion of disordered domains and a reduced portion of the most ordered domains. Further, sialyl Lewis X and/or A ligand-mediated adhesion of these cells was 2-fold enhanced. Confocal laser scanning microscopy further demonstrated a higher motility of ligands in the membrane of confluent cells, together with an accumulation of these ligands in distinct areas. Both facts are suggested to be responsible for an enhanced cell adhesion observed. Finally, an increased number of large distinct metastatic foci was registered in lungs of mice after i.v. inoculation of confluent cells. The results indicate that domain organization and fluidity of the cell membrane affect tumor cell adhesion and can have in this way also an impact on the malignancy of breast cancer cells.

Animals↗

PubMedDate not supplied

Spin label EPR-based characterization of biosystem complexity.

Following the widely spread EPR spin-label applications for biosystem characterization, a novel approach is proposed for EPR-based characterization of biosystem complexity. Hereto a computational method based on a hybrid evolutionary optimization (HEO) is introduced. The enormous volume of information obtained from multiple HEO runs is reduced with a novel so-called GHOST condensation method for automatic detection of the degree of system complexity through the construction of two-dimensional solution distributions. The GHOST method shows the ability of automatic quantitative characterization of groups of solutions, e.g. the determination of average spectral parameters and group contributions. The application of the GHOST condensation algorithm is demonstrated on four synthetic examples of different complexity and applied to two physiologically relevant examples--the determination of domains in biomembranes (lateral heterogeneity) and the study of the low-resolution structure of membrane proteins.

Algorithms↗

PubMedDate not supplied

Membrane switch hypothesis. 1. Cell density influences lateral domain structure of tumor cell membranes.

The domain structure of human cancer cells membranes was investigated by electron paramagnetic resonance (EPR) in different phases of cell growth, and the results were compared to those obtained for nonmalignant cells. On the basis of computer simulation of the EPR spectra using a newly developed GHOST condensation routine it was suggested that plasma membranes of cancer cells have less lateral lipid domain types at confluent conditions than in the exponential growing phase, while in nonmalignant cells the domain structure does not change significantly during cell growth. In accordance to our experimental data we propose a membrane switch hypothesis: disappearance of certain membrane domain types might act as a switch promoting the clustering of membrane constituents into the active units in a common lipid membrane domain and thus influencing the physiology of cells.

Cell Count↗

PubMedDate not supplied

Membrane switch hypothesis. 2. Domain structure of phagocytes in horses with recurrent airway obstruction.

The mechanism of recurrent airway obstruction (RAO) in horses was investigated by measuring the membrane domain structure and oxy-redoxy activity in phagocytes isolated from bronchoalveolar lavage fluid (BAL) and from the blood of healthy and RAO horses by electron paramagnetic resonance (EPR). Differences in the activity of intracellular antioxidant enzymes CAT, GPx, and SOD measured in phagocytes of RAO horses in comparison to healthy horses showed that the phagocytes were affected by oxidative stress. In comparison with polymorphonuclear leukocytes (phagocytes) from the blood of healthy horses the reduction mechanisms in BAL were faster and coincided with the merging of disordered membrane domains, while in horses with RAO the reduction and membrane domain structure remained unchanged. We assume that the merging of lipid domains observed in phagocytes from BAL of healthy horses could promote cluster formation of membrane proteins or ligands, which could trigger the activation process in phagocytes of healthy horses and consequently the physiological response that probably did not happen in phagocytes of RAO horses.

Airway Obstruction↗