Effects of curvature and topology on collective cell migration in dense biological tissues

Confluent epithelia line every organ surface and body cavity. The epithelial tissue typically remains quiescent and non-migratory while performing its routine barrier and immune functions but becomes dynamic and migratory during morphogenesis, repair, invasion and metastasis [1]. To model these processes, recent progress has been made using agent-based simulations [2] of multicellular behavior grown in cultures on flat space [3,4]. However, native epithelia typically comprise curved surfaces, such as embryos, and respiratory bronchioles, airways, intestines and embryos. On such curved geometry out-of-plane mechanical forces can influence cytoskeletal organization, cell-cell interaction and thus could influence migration and development. Here, we develop an agent-based cellular model to simulate the collective behavior on curved surfaces, such as spheres, ellipses and tubular structures. We explore how the curvature alters the nature of unjamming and glass transitions in tissues and how topological defects introduce new motion patterns.
[1] Sadati, M et al., Differentiation 2013
[2] Hakim & Silberzan, Rep on prog in phys 2017
[3] Park, J-A et al., Nat Mater 2015
[4] Atia, L. et al., Nat Phys 2018