Medizinische Klinik und Poliklinik I
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AG Gärtner

  • Cell- and mechanobiology of migrating cells – implications for cardiovascular biology

    General question

    1. How do cells control their shape and movement?
    2. How can we apply this knowledge to develop novel therapeutic strategies for the treatment of cardiovascular and inflammatory diseases?

    LMU Klinikum
    LMU Klinikum

    All immune cells, including platelets and leukocytes, are borne in the bone marrow before they enter the bloodstream to traverse the body and to monitor the organism for signs of danger. Throughout their journey, they encounter various mechanical challenges, including shear forces exerted by the bloodstream and tensile and compressive forces from the tissue microenvironment 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.

    LMU Klinikum

    Methods

    Our lab tackles these questions with a multidisciplinary approach that combines mouse genetics, microfluidics, quantitative microscopy and intravital imaging tools to study cell motility in physiological tissue environments. 

    Cell- and mechanobiology of platelet migration

    Despite lacking a nucleus, platelets are at the forefront of the mammalian immune response and constantly patrol the vasculature for signs of injury and inflammation. When a vessel springs a leak, platelets instantaneously get 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 ability to migrate which is required to guide them to sites of vascular injury and is essential for precise plugging of microlesions in inflamed blood vessels. However, the role of platelet migration reaches beyond hemostasis. Migrating platelets scan their environment for pathogenic invaders and pile up bacteria to prevent their dissemination within the organism.

    Our goal is to gain a better mechanistic understanding of this novel platelet function, which provides 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

    Homeostatic platelet counts are crucial for vascular integrity and vital to life. Megakaryocytes are giant hematopoietic cells forming large protrusions that fragment to constantly replenish the circulating platelet pool. Nevertheless, severe blood loss, infections and aggressive cancer therapies, often cause critically low platelet levels - a major public health problem of aging populations. Despite the unmet clinical need to control platelet production, there is a major lack of knowledge about the mechanistic cell biology of megakaryocytes, hampering the development of innovative therapies. To address this question, we integrate cell biological and biophysical tools to study megakaryocytes in physiological tissue environments to uncover the mechanical principles that drive platelet formation.