Anne Lagendijk

Cellular mechanisms to maintain a healthy vasculature

Our vascular system transports approximately 7500 liters of blood each day. Arteries deliver oxygen and nutrients throughout the body after which the venous system returns the deoxygenated blood back to the heart. Architecturally, these blood vessels are extremely heterogeneous. The Lagendijk group investigates the development and maintenance of a functional blood vessel network in zebrafish and bioengineered human microvessels. The cells that make up our blood vessels continuously adapt their size, adhesiveness and compliance order to ensure the right balance between vessel integrity and permeability in a context dependent manner. Mechanical cues play a major role in the functional adaptation of blood vessels. Despite ongoing research unraveling the structural components of mechanical hubs in the cells, it is essential to assess the magnitude of forces that are transduced at these sites and the biological consequences for vessel function. Dr. Lagendijk has previously developed a VE-cadherin tension biosensor line in zebrafish. This line provides the first vertebrate model that reports intra-molecular tension and was utilised to identify changes in junctional organisation and VE-cadherin tension that occur as arteries mature and revealed molecular pathways that allow for this maturation to happen. In addition, the lab has established disease models for vascular malformations that are known to lead to neurological deficits and stroke. Modelling in zebrafish allows analyses of the initiating mechanisms of these vascular pathologies at unprecedented cellular and subcellular resolution.