RT Journal Article
SR Electronic
T1 Mechanical cell competition in heterogeneous epithelial tissues
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 869495
DO 10.1101/869495
A1 R. J. Murphy
A1 P. R. Buenzli
A1 R. E. Baker
A1 M. J. Simpson
YR 2020
UL http://biorxiv.org/content/early/2020/05/24/869495.abstract
AB Mechanical cell competition is important during tissue development, cancer invasion, and tissue ageing. Heterogeneity plays a key role in practical applications since cancer cells can have different cell stiffness and different proliferation rates than normal cells. To study this phenomenon, we propose a one-dimensional mechanical model of heterogeneous epithelial tissue dynamics that includes cell-length-dependent proliferation and death mechanisms. Proliferation and death are incorporated into the discrete model stochastically and arise as source/sink terms in the corresponding continuum model that we derive. Using the new discrete model and continuum description, we explore several applications including the evolution of homogeneous tissues experiencing proliferation and death, and competition in a heterogeneous setting with a cancerous tissue competing for space with an adjacent normal tissue. This framework allows us to postulate new mechanisms that explain the ability of cancer cells to outcompete healthy cells through mechanical differences rather than by having some intrinsic proliferative advantage. We advise when the continuum model is beneficial and demonstrate why naively adding source/sink terms to a continuum model without considering the underlying discrete model may lead to incorrect results.Competing Interest StatementThe authors have declared no competing interest.