Characterization of endothelial cell locomotion using a Markov chain model.

A Markov chain model was developed to characterize the two-dimensional locomotion of bovine pulmonary artery endothelial (BPAE) cells cultured with or without basic fibroblast growth factor (bFGF). This model provides a detailed description of the migration process by computing the following locomotory parameters: (i) the speed of cell locomotion; (ii) the expected duration of cell movement in any given direction; (iii) the probability distribution of turn angles that will decide the next direction of cell movement; (iv) the frequency of cell stops; and (v) the duration of cell stops. Eight directional states and a stationary state were used in our Markov analysis. From cell trajectory data, the transition probabilities among the various states and the waiting times for the directional and the stationary states were computed. The steady-state probabilities were also calculated to obtain the ultimate direction of cell motion and, thus, determine whether cell motion was random. Our results showed how the addition of bFGF enhanced the locomotory capability of BPAE cells. Cells cultured with 30 ng/mL bFGF had lower probability of moving to the stationary state than those cultured without bFGF. In addition, cells cultured with 30 ng/mL bFGF remained in the stationary state for shorter periods of time than cells cultured without bFGF. In both these cases, however, the transition probabilities from the stationary state to any directional state were uniformly distributed and were not affected by the presence of bFGF.

[1]  Dunn Ga,et al.  Characterising a kinesis response: time averaged measures of cell speed and directional persistence. , 1983 .

[2]  B. Pauli,et al.  Quantitative analysis of autocrine-regulated, matrix-induced, and tumor cell-stimulated endothelial cell migration using a silicon template compartmentalization technique. , 1992, Experimental cell research.

[3]  A. F. Nind Neutrophil chemotaxis: technical problems with nitrocellulose filters in Boyden-type chambers. , 1981, Journal of immunological methods.

[4]  J. Abecassis,et al.  A Simple In Vitro Model of Mechanical Injury of Confluent Cultured Endothelial Cells to Study Quantitatively the Repair Process , 1986, Thrombosis and Haemostasis.

[5]  Richard B. Dickinson,et al.  Optimal estimation of cell movement indices from the statistical analysis of cell tracking data , 1993 .

[6]  Benoit B. Mandelbrot,et al.  Fractal Geometry of Nature , 1984 .

[7]  K Zygourakis,et al.  Analysis of endothelial cell locomotion: Differential effects of motility and contact inhibition , 1994, Biotechnology and bioengineering.

[8]  R. Ma,et al.  Endothelial regeneration. III. Time course of intimal changes after small defined injury to rat aortic endothelium. , 1981 .

[9]  Stuart K. Williams,et al.  Migration of individual microvessel endothelial cells: stochastic model and parameter measurement. , 1991, Journal of cell science.

[10]  S. Boyden THE CHEMOTACTIC EFFECT OF MIXTURES OF ANTIBODY AND ANTIGEN ON POLYMORPHONUCLEAR LEUCOCYTES , 1962, The Journal of experimental medicine.

[11]  D. Rifkin,et al.  Correlation of cell migration, cell invasion, receptor number, proteinase production, and basic fibroblast growth factor levels in endothelial cells , 1990, The Journal of cell biology.

[12]  Abraham Boyarsky A Markov chain model for human granulocyte movement , 1975 .

[13]  Douglas A. Lauffenburger,et al.  Measurement of individual cell migration parameters for human tissue cells , 1992 .

[14]  K Zygourakis,et al.  Proliferation of anchorage‐dependent contact‐inhibited cells: I. Development of theoretical models based on cellular automata , 1991, Biotechnology and bioengineering.

[15]  Schwartz Sm,et al.  Endothelial regneration. I. Quantitative analysis of initial stages of endothelial regeneration in rat aortic intima. , 1978 .

[16]  H. Cottier,et al.  Re-assessment of Boyden's technique for measuring chemotaxis. , 1972, JIM - Journal of Immunological Methods.

[17]  K Zygourakis,et al.  Quantification and regulation of cell migration. , 1996, Tissue engineering.

[18]  Measurement of phenomenological parameters for leukocyte motility and chemotaxis. , 1983, Agents and actions. Supplements.

[19]  B. Weksler,et al.  Inhibition of Leukocyte Migration by a Staphylococcal Factor , 1969, Journal of bacteriology.

[20]  M. Majesky Neointima formation after acute vascular injury. Role of counteradhesive extracellular matrix proteins. , 1994, Texas Heart Institute journal.

[21]  D. Rifkin,et al.  Autocrine activities of basic fibroblast growth factor: regulation of endothelial cell movement, plasminogen activator synthesis, and DNA synthesis , 1988, The Journal of cell biology.

[22]  M H Gail,et al.  The locomotion of mouse fibroblasts in tissue culture. , 1970, Biophysical journal.

[24]  Athanasios Papoulis,et al.  Probability, Random Variables and Stochastic Processes , 1965 .

[25]  D. Lauffenburger,et al.  The motile response of alveolar macrophages. An experimental study using single-cell and cell population approaches. , 1989, The American review of respiratory disease.

[26]  Sally H. Zigmond,et al.  Leukocyte locomotion and chemotaxis. New methods for evaluation, and demonstration of a cell-derived chemotactic factor. , 1973 .

[27]  S. Schwartz,et al.  Maintenance of integrity in aortic endothelium. , 1980, Federation proceedings.

[28]  E. Heber-Katz,et al.  Use of a solid-phase 3H-radioimmunoassay for the measurement of immunoglobulin produced in short-term cultures of antibody-secreting cells. , 1982, Journal of immunological methods.

[29]  R. Ross The pathogenesis of atherosclerosis: a perspective for the 1990s , 1993, Nature.

[30]  H. Berg Random Walks in Biology , 2018 .

[31]  K Zygourakis,et al.  A cellular automaton model for the proliferation of migrating contact-inhibited cells. , 1995, Biophysical journal.

[32]  P. Noble,et al.  A Markov chain characterization of human neutrophil locomotion under neutral and chemotactic conditions. , 1977, Canadian journal of physiology and pharmacology.

[33]  H. Gruler,et al.  Analysis of cell movement. , 1984, Blood cells.

[34]  D. Rifkin,et al.  In vitro angiogenesis on the human amniotic membrane: requirement for basic fibroblast growth factor-induced proteinases , 1989, The Journal of cell biology.

[35]  P. Markenscoff,et al.  Proliferation of anchorage‐dependent contact‐inhibited cells. II: Experimental results and validation of the theoretical models , 1991, Biotechnology and bioengineering.

[36]  R. A. Clark,et al.  Granulocyte chemotaxis: an improved in vitro assay employing 51 Cr-labeled granulocytes. , 1973, Journal of immunology.

[37]  Kenneth Falconer,et al.  Fractal Geometry: Mathematical Foundations and Applications , 1990 .

[38]  K. Leong,et al.  Fibroblast and hepatocyte behavior on synthetic polymer surfaces. , 1991, Journal of biomedical materials research.

[39]  L. Munn,et al.  Analysis of lymphocyte aggregation using digital image analysis. , 1993, Journal of immunological methods.

[40]  P. Noble,et al.  A two-dimensional random-walk analysis of human granulocyte movement. , 1972, Biophysical journal.

[41]  A. Clowes,et al.  Restenosis after vascular reconstruction. , 1994, Annals of medicine.