Document Type
Dissertation
Date of Award
1976
Keywords
Cytology, Research, Data processing, Cell populations, Cell migration
Degree Name
Doctor of Philosophy (PhD)
Department
Computer Science
First Advisor
Narenda Goel Chairman
Second Advisor
Peter Donovick
Third Advisor
Donald Gause
Abstract
When mixed aggregates of two appropriately different populations of vertebrate embryonic cells are allowed to move within a medium, one cell type will begin to segregate into small, randomly distributed internal clusters while the cells of the second population will form an external surrounding shell. This sorting-out phenomenon will continue until the internal aggregates become concentrated in a small number of large islands and sometimes a single cluster. The final state where one cell type surrounds an aggregate of the other cell type can be reached from radically different initial configurations, such as allowing tissue masses of both cell types to touch at one point. The final configuration is attained as the external tissue mass engulfs, or spreads around, the internal tissue mass. A hypothesis has been proposed by Steinberg, called the differential adhesion hypothesis, which explains these rearrangements in terms of motile and mutually adhesive cell populations which progress toward configurations of minimal adhesive free energy. Considerable experimental work has been conducted which supports this hypothesis. A mathematical model based on the differential adhesion hypothesis has been developed by Goel et al. which predicts the equilibrium configurations different cell populations can assume. Computer models, using the mathematical model as their framework, have had partial success simulating the phenomenon of cell sorting but have failed to simulate engulfment.
A computer model is described here which is able to simulate the morphogenetic cell rearrangements required to generate the predicted configurations from any initial state, in either two or three dimensions of one or more isotropic cell types, defined by a set of adhesive parameters, in a medium. This computer model, which also uses the mathematical model as its framework, treats simulated cellular systems a like systems of immiscible liquids, and uses the same motility rule for all simulated configurations. The model has been used to test the validity of the differential adhesion hypothesis in conjunction with different motility rules and to provide crucial information relating to the dynamics of the cellular spaces as they progress toward equilibrium configurations.
Specifically, the computer model has been used to simulate the following phenomena: (1) engulfment of two tissues of equal and unequal sizes; (2) engulfment of three tissues; (3) transition from an eccentric engulfed state to a concentric engulfed state; (4) rounding up of uneven tissue; (5) differentiation using time dependent adhesive parameters; (6) sorting-out of mixed aggregates of binary cell populations; (7) movement of single cells within solid tissue masses; (8) contact inhibition. The results of these simulations are consistent with experimental observations.
In addition, a software/hardware package has been developed which allows the visual display of tissue movement on a television screen, with various tissues represented by different colors.
Recommended Citation
Rogers, Gary, "Computer simulations of cellular movements" (1976). Graduate Dissertations and Theses. 334.
https://orb.binghamton.edu/dissertation_and_theses/334