A multiscale model of complex endothelial cell dynamics in early angiogenesis

Area of Science:

• Computational Biology
• Biophysics
• Vascular Biology

Background:

• Angiogenesis is crucial for development and disease, involving endothelial cell (EC) migration and network formation.
• Recent studies emphasize the role of EC rearrangements in shaping angiogenic networks.
• Existing models often lack the capacity to fully capture dynamic cell behaviors and environmental interactions.

Purpose of the Study:

• To introduce a novel hybrid 2D multiscale model of angiogenesis incorporating heterogeneous EC responses and cell rearrangements.
• To investigate the impact of cell rearrangements and gene expression on vascular network architecture.
• To identify potential biomarkers for pathological angiogenesis.

Main Methods:

• Developed a hybrid two-dimensional multiscale computational model for angiogenesis.
• Incorporated heterogeneous endothelial cell (EC) responses to microenvironmental cues and cell-cell interactions.
• Introduced a 'mixing measure' to quantify cell rearrangement during network formation and validated against experimental data.

Main Results:

• The model successfully reproduces characteristic angiogenic sprouting features like branching, chemotaxis, and cell mixing.
• Cell rearrangements were found to be directly correlated with vascular branching patterns, supporting their essential role in angiogenesis.
• Lower cell rearrangement predicts an imbalance between branching and sprout elongation, suggesting a link to pathological angiogenesis.

Conclusions:

• Cell rearrangements, driven by heterogeneous EC responses, are fundamental to sprouting angiogenesis and vascular network formation.
• The 'mixing measure' serves as a potential biomarker for pathological angiogenesis, computable from individual cell trajectories.
• The model provides a platform for predicting how genetic and environmental factors influence vascular network development.