AG Gärtner

All immune cells, including platelets and leukocytes, are formed in the bone marrow before they enter the bloodstream to circulate through the body and monitor the organism for signs of danger. On their journey, they are subjected to various mechanical challenges, including shear forces exerted by the bloodstream and tensile and compressive forces from the tissue microenvironment, which they actively monitor. This makes their seemingly effortless movement through the body all the more astonishing and raises the fundamental question of how cells control their shape and movement in tissue environments.

Cell and mechanobiology of platelet migration

Despite not having a nucleus, platelets are at the forefront of the mammalian immune response, constantly patrolling the vasculature to detect signs of injury and inflammation. When a vessel leaks, platelets are immediately activated and seal the lesion by forming a plug - a process required to maintain vascular integrity during inflammation. We have shown that platelets have the migratory capacity required to direct them to sites of vascular injury and are essential for the precise closure of micro-injuries in inflamed blood vessels. However, the role of platelet migration goes beyond hemostasis. Migrating platelets scan their environment for pathogenic invaders and accumulate bacteria to prevent their spread in the organism.

Our goal is to gain a better mechanistic understanding of this novel platelet function, which offers a unique opportunity to develop new and more specific therapeutic strategies for the treatment or prevention of thrombotic and infectious diseases.

Cell mechanics of megakaryocytes in 3D tissues

A homeostatic platelet count is critical for vascular integrity and vital. Megakaryocytes are giant hematopoietic cells that form large protrusions that fragment to constantly replenish the circulating platelet pool. Yet severe blood loss, infections and aggressive cancer therapies often result in critically low platelet levels - a major public health problem for ageing populations. Despite the unmet clinical need to control platelet production, there is a major lack of knowledge about the mechanistic cell biology of megakaryocytes, which hampers the development of innovative therapies. To address this issue, we are integrating cell biological and biophysical tools to study megakaryocytes in physiological tissue environments and uncover the mechanistic principles that govern platelet formation.