A mechanobiological model of endothelial cell migration and proliferation

Abstract

How angiogenesis is regulated by local environmental cues is still not fully understood despite its importance to many regenerative events. Although mechanics is known to influence angiogenesis, the specific cellular mechanisms influenced by mechanical loading are poorly understood. This study adopts a lattice-based modelling approach to simulate endothelial cell (EC) migration and proliferation in order to explore how mechanical stretch regulates their behaviour. The approach enables the explicit modelling of ECs and, in particular, their migration/proliferation (specifically, rate and directionality) in response to such mechanical cues. The model was first used to simulate previously reported experiments of EC migration and proliferation in an unloaded environment. Next, three potential effects (increased cell migration, increased cell proliferation and biased cellular migration) of mechanical stretch on EC behaviour were simulated using the model and the observed changes in cell population characteristics were compared to experimental findings. Combinations of these three potential drivers were also investigated. The model demonstrates that only by incorporating all three changes in cellular physiology (increased EC migration, increased EC proliferation and biased EC migration in the direction perpendicular to the applied strain) in response to dynamic loading, it is possible to successfully predict experimental findings. This provides support for the underlying model hypotheses for how mechanics regulates EC behaviour.

Keywords::

• endothelial cell
• migration
• proliferation
• mechanoregulation
• computational model
• angiogenesis

Additional information

Funding

This study was funded by Science Foundation Ireland under the President of Ireland Young Researcher Award [08/Y15/B1336] and through a Trinity College Dublin Research Studentship Award. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.