Welcome to the website of the Vorselen Lab of mechanobiology and quantitative immune cell biology!
What we do
In the Vorselen Lab, we are fascinated by regulation of cell functions by physical forces. We focus on our immune system, where immune cells use forces to guide target selection and enhance target killing. Many immune responses, such as eating (macrophage phagocytosis) and chemical killing (T cell cytotoxicity) of bacterial invaders and damaged or diseased cells, are more efficient for stiff than soft targets. Cancer cells are generally softer than healthy tissue cells, raising the possibility that they use their low rigidity as a means to evade the immune system. We focus both on the detailed mechanisms of regulation by physical forces in immune cells, as well as the consequences in the context of disease (e.g. cancer).
A special focus of our lab is macrophage mechanobiology. Macrophage are often abundantly present in tumors, although often in functions where they help the tumor. Reprogramming and targeting macrophages to induce cancer cell killing is therefore an attractive new therapeutic strategy. Revealing how macrophage responses are affected by physical cues may facilitate the design of novel therapeutics targeting completely new pathways in macrophages. Since the molecular machinery in many immune effector functions is shared, understanding macrophage eating (phagocytotis) may, for example, also gives fundamental insight into other immune cell responses.
Our mechanistic studies focus on how immune cells sense and generate forces, and how they integrate these signals with chemical signals they receive. We develop new biophysical approaches to tune the physical input that cells receive and new methods to measure cellular forces. A key contribution is our development (done during my time with Prof. Julie Theriot) of a “stress ball for the cell”: soft hydrogel microspheres that can be functionalized to trigger a variety of immune responses. They are tunable, uniquely model key physical characteristics of cancer cells (frequently used models are 10 million-fold(!) more rigid than cells), and can be kneaded and squeezed by cells, which renders them as cellular force sensors. We combine these techniques with quantitative microscopy and cellular perturbations (genetic, pharmaceutical) to interrogate how cells sense, and how they adapt their responses to the diverse threats they encounter. Together, this provides an unusual quantitative readout of immune cell behavior and helps us understand the regulation of immune processes by physical forces.
To study the consequences of macrophage mechanobiology in disease, we study how the broader macrophage response (signaling, cross-talk with adaptive immunity) is affected by mechanical input, and the role of macrophage mechanobiology in complex cell systems and (tumor) disease models.
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