Cellular mechanisms to maintain a healthy vasculature

Understanding how a heterogenous blood vessel network is established and maintained, providing insights in how we can tailor these different vessel types for therapeutic purposes

We are interested in how our blood vessel system is formed during embryonic development and how function of the system is maintained throughout life.

Arteries, veins and capillaries are architecturally extremely heterogeneous. The endothelial cells (ECs), that make up the inner lining of all these vessels types, need to continuously adapt their size, adhesiveness, compliance and ECM composition in order to ensure the right balance between vessel integrity and permeability.

Mechanical cues play a major role in the differentiation and functional adaptation of ECs and aberrant physical cues have been implicated in vascular diseases, like vascular malformations, atherosclerosis and hypertension. Studies in cultured ECs revealed that the adhesion molecule Vascular Endothelial (VE)-cadherin can function as a receptor for force at cell-cell junctions. At the cell-matrix interface, Integrin adhesion molecules perform a similar mechanoreceptor function.

Dr. Lagendijk previously developed a VE-cadherin tension biosensor line in zebrafish. This line reports intra-molecular tension across VE-cadherin live and was initially utilised to identify changes in junctional organization and VE-cadherin tension that occur as arteries mature and revealed molecular pathways that allow for this maturation to happen.

Currently, the lab is continuing on from this work by examining in more detail how force-bearing proteins control mechanical homeostasis of endothelial cells during vascular development, both at the cell-cell and the cell-matrix interface.

In addition, the lab has established disease models for vascular malformations that are known to lead to neurological deficits and stroke. Modelling in zebrafish and 3D engineered human vessels allows us to investigate the initiating mechanisms of these vascular pathologies at unprecedented cellular and subcellular resolution.