The ECM acts as a physical scaffold that binds cells together into tissues and guides cellular migration along matrix tracks, but it also presents a physical barrier that cells need to overcome �?either by proteolysis or by a shape change. The roles of the ECM and the influence of its specific features on cellular invasion are in the focus of current biomedical research, both in vivo and in vitro. Importantly, the ECM also elicits biochemical and biophysical signaling, which may influence cellular differentiation and motility. Migrating amoeboid cells are able to change their shape drastically in order to adapt to encountered constraints and thereby push through narrow places. These cells have low levels of integrin expression, reduced focal contacts, a low degree of adhesiveness and significantly higher motility velocities as compared to mesenchymal cells. Amoeboid shape-driven migration allows cells to evade, rather than degrade, barriers, and enables migration even when mesenchymal motility is impossible. Recent experimental work has shown that cells that were restricted to amoeboid motility, by inhibition of matrix metalloproteases could still invade pores that were as small as the nuclear size of the cell. New evidence also supports a central role for amoeboid motility in cell migration and cancer cell invasion. One consequence of this fact is that treatment by MMP inhibitors was found to be of low effectiveness against cancer metastases. In order to gain a deeper understanding of amoeboid motion in complex environments, we focused in this work on cellular navigation between obstacles. We first examined the influence of noise on cellular motion. In our stochastic compass model, the internal direction of the cell reflects the external gradient, with some added noise. The noise level scales inversely with the external gradient strength. This model feature is based on experimental results, showing increasing CI with increasing gradient steepness. Different noise levels can also result from internal cellular LEE011 citations characteristics. For example, normal cells exhibit a stronger response to specific growth factors compared to cancerous cells of the same cell line. This difference in gradient sensing between normal and cancer cells can therefore influence their ability to migrate, navigate and invade. By examining obstacle circumvention of amoeboid cells we show that cells can easily bypass obstacles of roughly their own size. This is a result of the noisy extensionretraction dynamics of membrane protrusions, which is the main characteristic of amoeboid motion. To challenge the cell‘s navigation ability, we placed the cells in a maze with contradictory cues. In most biological systems, the signaling molecules can diffuse through small pores in the tissue, while the larger cells need to bypass the obstacles, for example those posed by the ECM, as described above.