Nanoagents for manipulation of cell-ECM interaction

Collective cell invasion, e.g., of invasive tumors, and cell migration are determined by interactions of cells with their surroundings. The mechanical properties of the cell surroundings strongly influence these interactions. To investigate this influence of the mechanical properties, we will use methods that we have developed previously to structure the cell surroundings and control its mechanical properties. Furthermore, we have developed a method to control proteins, which sense and translate extracellular mechanical cues inside the cell, with light instead of mechanics. We will refine these techniques for structuring and optical protein control and apply them to study the influence of the mechanical properties of the cell surroundings on collective cell invasion into the surroundings. From this study we expect to gain an understanding on invasion of tumors and how it is influenced by the properties of the surrounding tissue.

Invasion of tumor cells from a tumor into its surroundings is determined by interactions of the tumor cells with their environment. Next to the chemical and biological properties, also the mechanical properties of the tumor environment strongly influence these interactions. In this project, we investigated the influence of tumor cell and environment properties, particularly its mechanical properties, on invasion. We used spheroids of tumor cells embedded in collagen as model system and developed techniques to control the mechanical properties of the collagen as model tumor environment. With this model system, we performed a detailed, quantitative analysis of the influence of collagen and spheroid properties on invasion of the spheroid into the collagen. The results revealed that the influence of the properties of the tumor environment does not only impact the extent of invasion, but may also bear implications on the activity of pharmacological inhibitors of invasion. These implications of the properties of the tumor environment on the activity of pharmacological inhibitors are planned to be addressed in more detail in future work of our lab, since it may be important for drug testing and for a better understanding of the activity of drugs and with that it may be supporting the development of therapies.