Z. Stachura

Cancer cell recognition--mechanical phenotype.

The major characteristics of cancer metastasis is the ability of the primary tumor cells to migrate by way of the blood or lymph vessels and to form tumors at multiple, distant sites. There are evidences that cancer progression is characterized by disruption and/or reorganization of cytoskeleton (i.e. cellular scaffold). This is accompanied by various molecular alterations influencing the overall mechanical resistance of cells. Current approach in diagnosis focuses mainly on microbiological, immunological, and pathological aspects rather than on the biomechanics of diseases. The determination of mechanical properties of an individual living cell has became possible with the development of local measurement techniques, such as atomic force microscopy, magnetic or optical tweezers. The advantage of them lies in the capability to measure living cells at a single cell level and in liquid conditions, close to natural environment. Here, we present the studies on mechanical properties of single cells originating from various cancers. The results show that, independently of the cancer type (bladder, melanoma, prostate, breast and colon), single cells are characterized by the lower Youngs modulus, denoting higher deformability of cancerous cells. However, the obtained Youngs modulus values were dependent on various factors, like the properties of substrates used for cell growth, force loading rate, or indentation depth. Their influence on elastic properties of cells was considered. Based on these findings, the identification of cancerous cells based on their elastic properties was performed. These results proved the AFM capability in recognition of a single, mechanically altered cell, also in cases when morphological changes are not visible. The quantitative analysis of cell deformability carried out using normal (reference) and cancerous cells and, more precisely, their characterization (qualitative and quantitative) can have a significant impact on the development of methodological approaches toward precise identification of pathological cells and would allow for more effective detection of cancer-related changes.

Cancer cell detection in tissue sections using AFM.

Currently, cancer diagnosis relies mostly on morphological examination of exfoliated, aspirated cells or surgically removed tissue. As long as standard diagnosis is concerned, this classical approach seems to be satisfactory. In the recent years, cancer progression has been shown to be accompanied by alterations in mechanical properties of cells. This offers the detection of otherwise unnoticed cancer cell disregarded by histological analysis due to insignificant manifestations. One of techniques, sensitive to changes in mechanical properties, is the atomic force microscopy, which detects cancer cells through their elastic properties. Such measurements were applied to tissue sections collected from patients suffering from various cancers. Despite of heterogeneity and complexity of cancer cell sections, the use of the Youngs modulus as an indicator of cell elasticity allow for detection of cancer cells in tissue slices.

Dose response and kinetics of foci disappearance following exposure to high- and low-LET ionizing radiation

Purpose: The effect of different radiation qualities on (i) 53BP1 (p53 Binding Protein 1) and p-ATM (phosphorylated ataxia telangiectasia mutated) foci induction, and (ii) on the kinetics of foci disappearance was analysed. Material and methods: Normal human skin fibroblasts were exposed to 240 kV broad-field X-rays or targeted with individually counted helium (3He) particles or protons (1H) from a Charged Particle Microbeam. Anti-p-ATM and anti-53BP1 antibodies were used for foci visualisation via immunocytochemistry. Results: 1 Gy of X-rays yielded ≈ 33 53BP1-positive foci/cell. The ratio between the number of delivered particles and yielded tracks was found to be 1:1 and 3:1 after targeted 3He and 1H irradiation, respectively. It was determined that ≈ 50% of radiation-induced damage was repaired as measured by loss of foci during the first 2, 6, and 10 hours following X-ray, protons, and 3He irradiation, respectively. Conclusions: There was significant radiation quality dependence for 53BP1- and p-ATM-positive foci induction observed. Foci disappearance was radiation dose-independent in the samples irradiated with X-rays. Our results confirm that kinetics of foci disappearance depends on radiation quality, even when individual ions are targeted to cells.

Probing nuclear properties by resonant atomic collisions between electrons and ions

The utilization of the resonant atomic electron–ion collision process of dielectronic recombination (DR) as a tool to probe nuclear properties via isotope shifts and hyperfine effects is discussed. Based on DR, this resonance reaction spectroscopy at electron coolers of heavy-ion storage rings denotes a versatile approach to access nuclear parameters such as charge radius, spin, magnetic moment or lifetimes of long-lived excited nuclear states (isomers). The high sensitivity of DR allows for experiments with artificially synthesized rare isotopes and isomers. Recent experimental progress in the preparation of such exotic species at the ESR storage ring in Darmstadt is presented. The DR technique is exemplified for the case of 234Pa88+ (Z = 91).

Isotope shifts in dielectronic recombination: From stable to in-flight-produced nuclei

The study of isotope shifts and hyperfine effects in dielectronic recombination (DR) resonance spectra strikes a conceptually new path for investigations of nuclear properties such as charge radius, spin, magnetic moment of nuclei or lifetimes of long-lived excited nuclear states. A series of DR experiments with heavy three-electron ions (Li-like) was performed at the heavy-ion storage ring ESR of the GSI Helmholtzzentrum fur Schwerionenforschung, Darmstadt, Germany. In a pilot experiment the two stable isotopes A=142 and A=150 of neodymium ANd57+ were investigated. From the displacement of DR resonances the isotope shifts δE142,150(2s – 2Pl/2) = 40.2(3)(6) meV and δE142,150(2s – 2p3/2) = 42.3(12)(20) meV for 2s – 2Pj transitions of the Li-like ions have been obtained. An evaluation within a full QED framework yielded a change in the mean-square charge radius of 142,150δ(r2) = −1.36(1)(3) fm2. At GSI, in addition to stable isotopes, in-flight synthesized radioisotopes can be studied as well. The production of radioisotopes of interest, the subsequent separation in the storage ring ESR and first DR experiments with the exotic nuclei 237U89+ and 234Pa88+ (Z=91) are presented. The paper is concluded with a brief outlook at future DR experiments with heavy radioisotopes at the ESR.

Electron bremsstrahlung in collisions of 223 MeV/ u He-like uranium ions with gaseous targets

The bremsstrahlung process in the domain of strong Coulomb fields has been investigated for and Ar target electrons colliding with He-like uranium ions at . The differential cross sections for bremsstrahlung were measured at laboratory observation angles of , , and . Substantial discrepancies were found between the experimental cross sections and the first-order Born approximation calculations. The reported data provide a new testing ground for non-perturbative treatment of the coupling between radiation and matter in the presence of strong fields.

Deviation from first-order perturbation theory observed at intermediate relativistic velocities for the ionisation of highly-charged heavy projectiles

Projectile K-shell ionization cross sections were measured for 80-200 MeV u-1 H- and He-like Bi ions on thin C, Al and Ni targets. The results are compared with predictions of first-order perturbation theories, RSCA and PWBA, as well as with experimental results published for Xe and U ions at similar ratios eta of projectile velocity to K-shell electron velocity. All experimental data lie a factor of 1.5 above theory for 0.6< eta <1.5.

Ground state transitions in one- and two-electron Bi projectiles

Abstract By using segmented solid state X-ray detectors and applying X-ray/charge-state selective particle coincidences, the ionic structures of 83 Bi 82+ and 83 Bi 81+ have been studied separately at 82 MeV/u under single collision conditions. The high granularity of the Ge(i) X-ray detectors used allowed a partial Doppler correction for the X-ray events while maintaining a large total solid angle. An absoluute precision of K-transition energies of 10 −3 is feasible; the relative accuracy is better than 30 eV. The experimental values compare very well with the theoretical transition energies in H- and He-like Bi ions.

Radiative recombination of bare Bi 83+ : Experiment versus theory

Electron-ion recombination of completely stripped Bi83+ was investigated at the Experimental Storage Ring (ESR) of the GSI in Darmstadt. It was the first experiment of this kind with a bare ion heavier than argon. Absolute recombination rate coefficients have been measured for relative energies between ions and electrons from 0 up to about 125 eV. In the energy range from 15 meV to 125 eV a very good agreement is found between the experimental result and theory for radiative recombination (RR). However, below 15 meV the experimental rate increasingly exceeds the RR calculation and at Erel = 0 eV it is a factor of 5.2 above the expected value. For further investigation of this enhancement phenomenon the electron density in the interaction region was set to 1.6E6/cm3, 3.2E6/cm3 and 4.7E6/cm3. This variation had no significant influence on the recombination rate. An additional variation of the magnetic guiding field of the electrons from 70 mT to 150 mT in steps of 1 mT resulted in periodic oscillations of the rate which are accompanied by considerable changes of the transverse electron temperature.

Projectile excitation and ionization in relativistic ion-atom collisions

Abstract K-shell ionization and excitation is studied for high-Z one-and two-electron ions in relativistic encounters with low-Z targets. For ionization, the data obtained for solid and gaseous targets are compared in detail with the predictions of first order perturbation theory. On the basis of the most recent experimental results, the systematic deviation from first order perturbation theory as observed recently for high-Z ions cannot be confirmed. Moreover, special emphasis is given to a dedicated experiment where projectile excitation has been studied in encounters of heavy one-and two-electron bismuth ions (Z = 83) with light solid targets. The measurement of the characteristic ground-state transitions in coincidence with the primary charge state allowed us to study the formation of excited projectile states via direct Coulomb excitation. In particular, due to the large fine-structure splitting, the excitation cross-sections for the various L-shell sublevels in H- and He-like bismuth could be determined separately. The results are compared with detailed relativistic calculations showing that for high-Z projectiles the magnetic interaction is of considerable importance at the considered collision energies.