Computational modeling of cell sorting, tissue engulfment, and related phenomena: A review

Abstract

Embryonic cells have the remarkable ability to spontaneously reposition themselves with respect to other cells in an aggregate, an ability that is central to embryo morphogenesis, many disease processes, wound healing, and tissue engineering. In these rearrangements, cells of two or more histological types in a heterotypic aggregate can sort, mix or form checkerboard patterns and contacting fragments of different homogeneous tissues can spread over or engulf one another. In this article, the experimental literature on cell and tissue reorganization is summarized, the main sub-cellular structural components are identified and hypotheses about how these components interact to drive specific patterns of rearrangement are outlined. Making extensive use of tables, the article then maps out the interplay between experiments, theories, ultrastructural discoveries and computer models in the advancement of the field. The article summarizes the main computational approaches, including cell and sub-cellular lattices, body centric, boundary vertex and finite element models. The principle of operation, advantages and disadvantages of each approach is discussed, and the contributions of representative papers noted. Strong commonalities are found in the physical basis of the models and in the predictions they make. Computational models provide an important ongoing complement to experimental and theoretical studies. This review article cites 154 references.