Computational model of cell positioning: directed and collective migration in the intestinal crypt epithelium.
The epithelium of the intestinal crypt is a dynamic tissue undergoing constant regeneration through cell growth, cell division, cell differentiation and apoptosis. How the epithelial cells maintain correct positioning and how they migrate in a directed and collective fashion are still not well understood. In this paper, we developed a computational model to elucidate these processes. We show that differential adhesion between epithelial cells, caused by the differential activation of EphB receptors and ephrinB ligands along the crypt axis, is necessary to regulate cell positioning. Differential cell adhesion has been proposed previously to guide cell movement and cause cell sorting in biological tissues. The proliferative cells and the differentiated post-mitotic cells do not intermingle as long as differential adhesion is maintained. We also show that, without differential adhesion, Paneth cells are randomly distributed throughout the intestinal crypt. In addition, our model suggests that, with differential adhesion, cells migrate more rapidly as they approach the top of the intestinal crypt. Finally, by calculating the spatial correlation function of the cell velocities, we observe that differential adhesion results in the differentiated epithelial cells moving in a coordinated manner, where correlated velocities are maintained at large distances, suggesting that differential adhesion regulates coordinated migration of cells in tissues.
Wong
Shek Yoon
SY
Computation and Systems Biology, Singapore-MIT Alliance, National University of Singapore, 4 Engineering Drive 3, Singapore 117576, Republic of Singapore.
Chiam
K-H
KH
Lim
Chwee Teck
CT
Matsudaira
Paul
P
D002448:Cell Adhesion / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology*; D019295:Computational Biology / Q000379:methods*; D003198:Computer Simulation; D007413:Intestinal Mucosa / Q000166:cytology*; D008954:Models, Biological; D036081:Receptors, Eph Family / Q000378:metabolism*
D036081:Receptors, Eph Family