Coherent vibration states in biological systems excited in nonlinear electrically polar structures by metabolic energy supply were postulated by H. Frohlich. Frohlich's requirements for coherent vibrations and generation of electromagnetic field are satisfied by microtubules whose subunits are electric dipoles. Static electric field around mitochondria and "wasted energy" efflux from them provide nonlinear conditions and coherent excitation. Numerical models are used for analysis of coherent vibration states. A hypothesis is presented that dysfunction of mitochondria (i.e., extinction of the zones of the static electric field and of the efflux of "wasted energy") and disintegration of the cytoskeleton on the pathway of cancer transformation result in disturbances of coherence of the cellular electrically polar oscillations and of the generated electromagnetic field with consequences in cellular organization and interactions between cells. Local invasion, detachment, and metastasis of cancer cells are subsequent events of disturbed electromagnetic interactions.
- MeSH
- Biophysical Phenomena MeSH
- Models, Biological MeSH
- Cytoskeleton metabolism radiation effects MeSH
- Electromagnetic Fields adverse effects MeSH
- Humans MeSH
- Mitochondria metabolism radiation effects MeSH
- Cell Transformation, Neoplastic MeSH
- Cell Line, Tumor MeSH
- Neoplasms pathology MeSH
- Nonlinear Dynamics MeSH
- Vibration MeSH
- Check Tag
- Humans MeSH
Mechanical interaction of cell with extracellular environment affects its function. The mechanisms by which mechanical stimuli are sensed and transduced into biochemical responses are still not well understood. Considering this, two finite element (FE) bendo-tensegrity models of a cell in different states are proposed with the aim to characterize cell deformation under different mechanical loading conditions: a suspended cell model elucidating the global response of cell in tensile test simulation and an adherent cell model explicating its local response in atomic force microscopy (AFM) indentation simulation. The force-elongation curve obtained from tensile test simulation lies within the range of experimentally obtained characteristics of smooth muscle cells (SMCs) and illustrates a nonlinear increase in reaction force with cell stretching. The force-indentation curves obtained from indentation simulations lie within the range of experimentally obtained curves of embryonic stem cells (ESCs) and exhibit the influence of indentation site on the overall reaction force of cell. Simulation results have demonstrated that actin filaments (AFs) and microtubules (MTs) play a crucial role in the cell stiffness during stretching, whereas actin cortex (AC) along with actin bundles (ABs) and MTs are essential for the cell rigidity during indentation. The proposed models quantify the mechanical contribution of individual cytoskeletal components to cell mechanics and the deformation of nucleus under different mechanical loading conditions. These results can aid in better understanding of structure-function relationships in living cells.
- MeSH
- Finite Element Analysis * MeSH
- Models, Biological * MeSH
- Biomechanical Phenomena MeSH
- Cytoskeleton metabolism MeSH
- Eukaryotic Cells cytology metabolism MeSH
- Mechanical Phenomena * MeSH
- Actin Cytoskeleton metabolism MeSH
- Microtubules metabolism MeSH
- Tensile Strength MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
Hypothesis of coherent vibration states in biological systems based on nonlinear interaction between longitudinal elastic and electric polarization fields with metabolic energy supply was formulated by Frohlich. Conditions for excitation of coherent states and generation of electromagnetic fields are satisfied in microtubules which form electrical polar structures. Numerical models are used for analysis of Frohlich's vibration states in cells. Reduction of activity and of energy production in mitochondria, and disintegration of cytoskeleton structures by phosphorylation on the pathway of cancer trasformation can diminish excitation of the Frohlich's vibration states and of the generated electromagnetic field, which results in disturbances of the interaction forces between cells. Interaction forces between cancer cells may be smaller than interaction forces between healthy cells and cancer cells as follows from numerical models. Mechanism of malignity, i.e. local invasion, detachment of cancer cells, and metastasis, is assumed to depend on the electromagnetic field.
- MeSH
- Biophysics methods MeSH
- Models, Biological MeSH
- 3T3 Cells MeSH
- Cytoskeleton metabolism MeSH
- Electromagnetic Fields MeSH
- Electromagnetic Phenomena MeSH
- Humans MeSH
- Microscopy, Atomic Force MeSH
- Microtubules metabolism MeSH
- Mitochondria metabolism MeSH
- Mice MeSH
- Neoplasms metabolism MeSH
- Elasticity MeSH
- Saccharomyces cerevisiae metabolism MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Review MeSH
OBJECTIVE: Individuals with decreased thiopurine methyltransferase (TPMT) activity are at risk of adverse effects of thiopurine administration whereas its increased activity may inactivate drugs faster. We evaluated genotype-phenotype correlations in patients with suspected hematological malignancies and inflammatory bowel disease from our region based on findings of nonlinear TPMT enzyme kinetics previously unreported. PATIENTS AND METHODS: The study group comprised 267 individuals. They were screened for the most common variants of low TPMT activity. TPMT activity was measured in erythrocytes using the HPLC rate-blanked method. RESULTS: Thirty-three patients (12.4%) were heterozygous (26 were TPMT*1/*3A, 5 TPMT*1/*2, 2 TPMT *1/*3C) and 1 was a compound heterozygote (*2/*3A). Normal and low normal TPMT activities substantially overlapped in wild-type and heterozygous individuals, whereas high activities were found in 29 wild-type genotyped patients. Extreme and life-threatening toxicity was observed in the compound heterozygote patient. CONCLUSION: Activity measurement performed at diagnosis provides clinicians with information on immediate pharmacokinetic-related adverse events and/or hypermetabolism, and genotyping may indicate the rate of pharmacodynamic thioguanine nucleotide accumulation due to slower overall thiopurine metabolism.
- MeSH
- Asparaginase therapeutic use MeSH
- Cyclophosphamide therapeutic use MeSH
- Cytarabine therapeutic use MeSH
- Daunorubicin therapeutic use MeSH
- Erythrocyte Membrane enzymology MeSH
- Genetic Association Studies MeSH
- Inflammatory Bowel Diseases blood MeSH
- Humans MeSH
- Precursor T-Cell Lymphoblastic Leukemia-Lymphoma drug therapy genetics MeSH
- Mercaptopurine therapeutic use MeSH
- Methotrexate therapeutic use MeSH
- Methyltransferases deficiency genetics metabolism MeSH
- Adolescent MeSH
- Polymerase Chain Reaction MeSH
- Prednisone therapeutic use MeSH
- Antineoplastic Combined Chemotherapy Protocols therapeutic use MeSH
- Vincristine therapeutic use MeSH
- Chromatography, High Pressure Liquid MeSH
- Check Tag
- Humans MeSH
- Adolescent MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Case Reports MeSH
- Research Support, Non-U.S. Gov't MeSH
- Geographicals
- Czech Republic MeSH
- Slovakia MeSH
