New View on Endothelial Cell Migration: Switching Modes of Migration Based on Matrix Composition

Area of Science:

• Cell Biology
• Biomaterials Science
• Developmental Biology

Background:

• Cell-matrix interactions regulate cellular activities like migration, vital for morphogenesis such as angiogenesis.
• Current understanding of cell migration predominantly relies on 2D models, with limited knowledge of endothelial cell (EC) behavior in 3D environments.
• The influence of matrix composition on EC migration in 3D settings remains largely unexplored.

Purpose of the Study:

• To investigate endothelial cell (EC) migration in distinct 3D matrix environments.
• To elucidate the role of matrix composition, specifically laminin, in modulating EC migration phenotypes.
• To explore the plasticity of EC migration in response to pharmacological inhibition.

Main Methods:

• Characterization of single EC migration in spongy Matrigel and fibrillar collagen I hydrogels.
• Utilized pharmacological inhibitors for Rac1, Cdc42, and proteolysis pathways.
• Employed anti-integrin antibodies and laminin supplementation to identify key molecular determinants.
• Performed in situ live imaging of EC migration during vascular growth in murine retina.

Main Results:

• ECs displayed distinct migration phenotypes: elongated in Matrigel and rounded with blebs in collagen I.
• Directed migration in collagen I depended on Rac1 and Cdc42, unlike in Matrigel.
• Laminin was identified as the primary determinant of the elongated phenotype in collagen I, inducing a migratory mode switch.
• In vivo experiments demonstrated ECs can evade migration pathway inhibition through mode switching.

Conclusions:

• Endothelial cells (ECs) exhibit remarkable plasticity, capable of switching migration modes to circumvent pharmacological inhibition of key signaling pathways.
• This adaptive behavior highlights the context-dependent nature of EC migration and its implications for angiogenesis.
• Findings challenge the predictive power of 2D models and emphasize the importance of 3D microenvironments in cell migration studies.