Computational models reveal a passive mechanism for cell migration in the crypt

TY - JOUR

T1 - Computational models reveal a passive mechanism for cell migration in the crypt

AU - Dunn, Sara-Jane

AU - Näthke, Inke S.

AU - Osborne, James M.

PY - 2013/11/18

Y1 - 2013/11/18

N2 - Cell migration in the intestinal crypt is essential for the regular renewal of the epithelium, and the continued upward movement of cells is a key characteristic of healthy crypt dynamics. However, the driving force behind this migration is unknown. Possibilities include mitotic pressure, active movement driven by motility cues, or negative pressure arising from cell loss at the crypt collar. It is possible that a combination of factors together coordinate migration. Here, three different computational models are used to provide insight into the mechanisms that underpin cell movement in the crypt, by examining the consequence of eliminating cell division on cell movement. Computational simulations agree with existing experimental results, confirming that migration can continue in the absence of mitosis. Importantly, however, simulations allow us to infer mechanisms that are sufficient to generate cell movement, which is not possible through experimental observation alone. The results produced by the three models agree and suggest that cell loss due to apoptosis and extrusion at the crypt collar relieves cell compression below, allowing cells to expand and move upwards. This finding suggests that future experiments should focus on the role of apoptosis and cell extrusion in controlling cell migration in the crypt.

AB - Cell migration in the intestinal crypt is essential for the regular renewal of the epithelium, and the continued upward movement of cells is a key characteristic of healthy crypt dynamics. However, the driving force behind this migration is unknown. Possibilities include mitotic pressure, active movement driven by motility cues, or negative pressure arising from cell loss at the crypt collar. It is possible that a combination of factors together coordinate migration. Here, three different computational models are used to provide insight into the mechanisms that underpin cell movement in the crypt, by examining the consequence of eliminating cell division on cell movement. Computational simulations agree with existing experimental results, confirming that migration can continue in the absence of mitosis. Importantly, however, simulations allow us to infer mechanisms that are sufficient to generate cell movement, which is not possible through experimental observation alone. The results produced by the three models agree and suggest that cell loss due to apoptosis and extrusion at the crypt collar relieves cell compression below, allowing cells to expand and move upwards. This finding suggests that future experiments should focus on the role of apoptosis and cell extrusion in controlling cell migration in the crypt.

KW - Animals

KW - cell division

KW - Cell movement

KW - cell proliferation

KW - cell size

KW - Computer simulation

KW - Intestinal Mucosa

KW - mice

KW - models

KW - biological

UR - https://www.scopus.com/pages/publications/84894148547

U2 - 10.1371/journal.pone.0080516

DO - 10.1371/journal.pone.0080516

M3 - Article

C2 - 24260407

AN - SCOPUS:84894148547

SN - 1932-6203

VL - 8

JO - PLoS ONE

JF - PLoS ONE

IS - 11

M1 - e80516

ER -