Quantifying cell-ECM adhesion by single cell force spectroscopy

Integrin-mediated adhesive interactions of cells with the extracellular matrix (ECM) regulate important cellular functions and play a critical role in disease. Therefore, studying the mechanisms underlying integrin-binding and regulation is of great interest. In the presented work three respective biological questions have been addressed using Atomic Force Microscopy based Single Cell Force Spectroscopy (AFM-SCFS). The work is split into six chapters. The first chapter provides an introduction into cell-ECM interactions. Thereafter different adhesion assays are compared and contrasted, and the theoretical Bell-Evans model is discussed. In chapter four, alpha2beta1-integrin mediated cell adhesion to collagen I is quantified. Thereafter the effects of the exposure of cryptic integrin binding sites within collagen I on pre-osteoblasts are analysed. At last, the role of BCR/ABL in modulating myeloid progenitor cell adhesion to stromal cells and ECM-coated substrates is studied. Taken together, the work demonstrates that AFM-SCFS is a versatile tool that permits monitoring of cell adhesion from single-molecule recognition events to the formation of more complex adhesion sites.