Biomedical subjects

Michael A Mackey

Publications and source records attributed to Michael A Mackey.

4 recordsLinked to original sources

PubMed2006

Ameboid cell motility: a model and inverse problem, with an application to live cell imaging data.

In this article a mathematical model for ameboid cell movement is developed using a spring-dashpot system with Newtonian dynamics. The model is based on the facts that the cytoskeleton plays a primary role for cell motility and that the cytoplasm is viscoelastic. Based on the model, the inverse problem can be posed: if a structure like a spring-dashpot system is embedded into the living cell, what kind of characteristic properties must the structure have in order to reproduce a given movement of the cell? This inverse problem is the primary topic of this paper. On one side the model mimics some features of the movement, and on the other side, the solution to the inverse problem provides model parameters that give some insight, principally into the mechanical aspect, but also, through qualitative reasoning, into chemical and biophysical aspects of the cell. Moreover, this analysis can be done locally or globally and in different media by using the simplest possible information: positions of the cell and nuclear membranes. It is shown that the model and solution to the inverse problem for simulated data sets are highly accurate. An application to a set of live cell imaging data obtained from random movements of a human brain tumor cell (U87-MG human glioblastoma cell line) then provides an example of the efficiency of the model, through the solution of its inverse problem, as a way of understanding experimental data.

Cell Membrane↗

PubMed2006

Lack of p53 function promotes radiation-induced mitotic catastrophe in mouse embryonic fibroblast cells.

BACKGROUND: We have demonstrated that in some human cancer cells both chronic mild heat and ionizing radiation exposures induce a transient block in S and G2 phases of the cell cycle. During this delay, cyclin B1 protein accumulates to supranormal levels, cyclin B1-dependent kinase is activated, and abrogation of the G2/M checkpoint control occurs resulting in mitotic catastrophe (MC). RESULTS: Using syngenic mouse embryonic fibroblasts (MEF) with wild-type or mutant p53, we now show that, while both cell lines exhibit delays in S/G2 phase post-irradiation, the mutant p53 cells show elevated levels of cyclin B1 followed by MC, while the wild-type p53 cells present both a lower accumulation of cyclin B1 and a lower frequency of MC. CONCLUSION: These results are in line with studies reporting the role of p53 as a post-transcriptional regulator of cyclin B1 protein and confirm that dysregulation of cyclin B1 promote radiation-induced MC. These findings might be exploited to design strategies to augment the yield of MC in tumor cells that are resistant to radiation-induced apoptosis.

Journal Article↗

PubMed2005

Cell segmentation, tracking, and mitosis detection using temporal context.

The Large Scale Digital Cell Analysis System (LSDCAS) developed at the University of Iowa provides capabilities for extended-time live cell image acquisition. This paper presents a new approach to quantitative analysis of live cell image data. By using time as an extra dimension, level set methods are employed to determine cell trajectories from 2D + time data sets. When identifying the cell trajectories, cell cluster separation and mitotic cell detection steps are performed. Each of the trajectories corresponds to the motion pattern of an individual cell in the data set. At each time frame, number of cells, cell locations, cell borders, cell areas, and cell states are determined and recorded. The proposed method can help solving cell analysis problems of general importance including cell pedigree analysis and cell tracking. The developed method was tested on cancer cell image sequences and its performance compared with manually-defined ground truth. The similarity Kappa Index is 0.84 for segmentation area and the signed border positioning segmentation error is 1.6 +/- 2.1 microm.

Algorithms↗

PubMed2004

Mitochondrial O2*- and H2O2 mediate glucose deprivation-induced stress in human cancer cells.

The hypothesis that glucose deprivation-induced cytotoxicity in transformed human cells is mediated by mitochondrial O2*- and H2O2 was first tested by exposing glucose-deprived SV40-transformed human fibroblasts (GM00637G) to electron transport chain blockers (ETCBs) known to increase mitochondrial O2*- and H2O2 production (antimycin A (AntA), myxothiazol (Myx), or rotenone (Rot)). Glucose deprivation (2-8 h) in the presence of ETCBs enhanced parameters indicative of oxidative stress (i.e. GSSG and steady-state levels of oxygen-centered radicals) as well as cytotoxicity. Glucose deprivation in the presence of AntA also significantly enhanced cytotoxicity and parameters indicative of oxidative stress in several different human cancer cell lines (PC-3, DU145, MDA-MB231, and HT-29). In addition, human osteosarcoma cells lacking functional mitochondrial electron transport chains (rho0) were resistant to glucose deprivation-induced cytotoxicity and oxidative stress in the presence of AntA. In the absence of ETCBs, aminotriazole-mediated inactivation of catalase in PC-3 cells demonstrated increases in intracellular steady-state levels of H2O2 during glucose deprivation. Finally, in the absence of ETCBs, overexpression of manganese containing superoxide dismutase and/or mitochondrial targeted catalase using adenoviral vectors significantly protected PC-3 cells from toxicity and oxidative stress induced by glucose deprivation with expression of both enzymes providing greater protection than was seen with either alone. Overall, these findings strongly support the hypothesis that mitochondrial O2*- and H2O2 significantly contribute to glucose deprivation-induced cytotoxicity and metabolic oxidative stress in human cancer cells.

Adenosine Triphosphate↗