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Jens O M Karlsson

Publications and source records attributed to Jens O M Karlsson.

5 recordsLinked to original sources

Kinetics of intracellular ice formation in one-dimensional arrays of interacting biological cells.

Although cell-cell interactions are known to significantly affect the kinetics of intracellular ice formation (IIF) during tissue freezing, this effect is not well understood. Progress in elucidating the mechanism and role of intercellular ice propagation in tissue freezing has been hampered in part by limitations in experimental design and data analysis. Thus, using rapid-cooling cryomicroscopy, IIF was measured in adherent cells cultured in micropatterned linear constructs (to control cell-cell interactions and minimize confounding factors). By fitting a Markov chain model to IIF data from micropatterned HepG2 cell pairs, the nondimensional rate of intercellular ice propagation was found to be alpha = 10.4 +/- 0.1. Using this measurement, a new generator matrix was derived to predict the kinetics of IIF in linear four-cell constructs; cryomicroscopic measurements of IIF state probabilities in micropatterned four-cell arrays conformed with theoretical predictions (p < 0.05), validating the modeling assumptions. Thus, the theoretical model was extended to allow prediction of IIF in larger tissues, using Monte Carlo techniques. Simulations were performed to investigate the effects of tissue size and ice propagation rate, for one-dimensional tissue constructs containing up to 100 cells and nondimensional propagation rates in the range 0.1 < or = alpha < or = 1000.

Calibration↗

Theoretical analysis of unidirectional intercellular ice propagation in stratified cell clusters.

A recently published theoretical analysis of intercellular ice propagation in stratified cell clusters comprising concentric spherical layers, by Zhang, Xu, Sandison, and Zhang [Cryobiology 47 (2003) 143], has been examined and is shown to be flawed. New equations are derived subject to simplifying assumptions implicit in the theoretical model presented by Zhang and co-workers. The conclusion by Zhang and colleagues that intercellular ice propagation can be assumed to be instantaneous is demonstrated to be invalid.

Algorithms↗

Parametric analysis of intercellular ice propagation during cryosurgery, simulated using monte carlo techniques.

A microscale theoretical model of intracellular ice formation (IIF) in a heterogeneous tissue volume comprising a tumor mass and surrounding normal tissue is presented. Intracellular ice was assumed to form either by intercellular ice propagation or by processes that are not affected by the presence of ice in neighboring cells (e.g., nucleation or mechanical rupture). The effects of cryosurgery on a 2D tissue consisting of 10(4) cells were simulated using a lattice Monte Carlo technique. A parametric analysis was performed to assess the specificity of IIF-related cell damage and to identify criteria for minimization of collateral damage to the healthy tissue peripheral to the tumor. Among the parameters investigated were the rates of interaction-independent IIF and intercellular ice propagation in the tumor and in the normal tissue, as well as the characteristic length scale of thermal gradients in the vicinity of the cryosurgical probe. Model predictions suggest gap junctional intercellular communication as a potential new target for adjuvant therapies complementing the cryosurgical procedure.

Cell Line, Tumor↗

Kinetics and mechanism of intercellular ice propagation in a micropatterned tissue construct.

Understanding the effects of cell-cell interaction on intracellular ice formation (IIF) is required to design optimized protocols for cryopreservation of tissue. To determine the effects of cell-cell interactions during tissue freezing, without confounding effects from uncontrolled factors (such as time in culture, cell geometry, and cell-substrate interactions), HepG2 cells were cultured in pairs on glass coverslips micropatterned with polyethylene glycol disilane, such that each cell interacted with exactly one adjacent cell. Assuming the cell pair to be a finite state system, being either in an unfrozen state (no ice in either cell), a singlet state (IIF in one cell only), or a doublet state (IIF in both cells), the kinetics of state transitions were theoretically modeled and cryomicroscopically measured. The rate of intercellular ice propagation, estimated from the measured singlet state probability, increased in the first 24 h of culture and remained steady thereafter. In cell pairs cultured for 24 h and treated with the gap junction blocker 18beta-glycyrrhetinic acid before freezing, the intercellular ice propagation rate was lower than in untreated controls (p < 0.001), but significantly greater than zero (p < 0.0001). These results suggest that gap junctions mediate some, but not all, mechanisms of ice propagation in tissue.

Biophysical Phenomena↗