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Our bodies contain an extensive network of blood vessels. This network transports oxygen and nutrients to organs, tissues, and cells while also removing waste products. During development and throughout life, the body forms new blood vessels through a process called angiogenesis. This process is essential for maintaining healthy tissues. When angiogenesis is disrupted, it can contribute to diseases such as cancer and vascular disorders.

Despite its importance, scientists still do not fully understand how new blood vessels form. As a result, opportunities to repair damaged tissues or create new tissues remain limited.

Blood vessel formation is controlled by endothelial cells, the cells that line the inside of blood vessels. During angiogenesis, these cells take on different roles. Some become tip cells, which lead the growth of a new blood vessel and determine its direction. Others become stalk cells, which build and support the structure of the growing vessel. The timing of this decision is crucial, as it helps determine how the blood vessel network develops.

Mechanical signals shape blood vessel growth

Previous studies mainly focused on the chemical signals that guide this process. However, growing evidence suggested that physical properties of the cellular environment, such as the stiffness or softness of surrounding tissue, may also play an important role.

To better understand these effects, Passier developed a series of computational models.

Her work focused on the proteins YAP and TAZ, which help cells sense and respond to mechanical signals from their environment. She investigated how YAP/TAZ interact with NOTCH, a signaling system that plays a key role in determining whether a cell becomes a tip cell or a stalk cell during angiogenesis.

The models showed that tissue stiffness affects how quickly endothelial cells decide which identity to adopt. The speed of this decision in turn influences the structure of the developing blood vessel network.

The findings indicate that the mechanical properties of biomaterials can be used to direct angiogenesis in both time and space. This is particularly relevant for tissue engineering, a field focused on repairing or replacing damaged tissues.

New insights into vascular disease

The simulations also provided insight into what may go wrong in certain diseases.

According to the models, disrupted cell signaling can delay the decision between tip cell and stalk cell identities. Such delays may contribute to the abnormal blood vessel structures that are characteristic of some disorders.

The results further suggested that influencing the activity of YAP/TAZ may help restore disrupted vascular structures. These findings provide promising directions for future research.

The study also showed that tissue stiffness is not the only physical factor that matters. Differences in cell size and small mechanical forces generated when cells interact with one another were also found to affect angiogenesis.

For example, differences in size between individual cells could accelerate the process by which cells choose their identities. At the same time, the simulations showed that angiogenesis can be disrupted when all cells become excessively enlarged.

Toward better control of blood vessel formation

The findings of Passier's dissertation demonstrate that mechanical factors play a crucial role in the formation of new blood vessels. Tissue stiffness, differences in cell size, and forces between cells all influence how endothelial cells choose their roles during angiogenesis.

Together, these insights improve our understanding of how healthy blood vessel networks develop and why this process can become disrupted in disease. They also point to new possibilities for controlling blood vessel growth, particularly in the development of biomaterials and engineered tissues.