Patterning of cell-to-cell variability through cross talk between cell adhesion and endocytosis
Final Report Abstract
This study should have been the first to investigate integrin receptor expression and signalling as well as extracellular matrix composition as elements of cell-matrix adhesion by analysis of cell-to-cell variability. I am convinced that such analysis could reveal new regulatory mechanisms, which will increase our understanding of cell-matrix adhesion at the fundamental level. I think that particularly parameters of the cell's microenvironment, such as the local cell density and the relative localisation of a cell within a population, are important determinants of cell-to-cell variability in cell-matrix adhesion. In turn the strength of cell-matrix adhesion can create cell-to-cell variability in other processes. Retrospectively, I think however that the project was very ambiguous and the scope was too wide for a 2 years period. In addition several unexpected technical problems occurred with in my eyes established methods and would have made it necessary to invest more time and get more people involved, particularly in terms of data analysis. Effort for and deferment in the establishment of experimental multiplexing also had some impact on the project. Nevertheless this new technique may have been used in the project at a later time point again and thus could still have contributed to the project. Some of the preliminary results were very promising. Repetition of some experiments to have enough biological replicates would already have led to the first set of final results, describing patterns of cell-to-cell variability in ECM protein expression. Initial time lapse experiments were particularly interesting, indicating a time- and microenvironment-dependent deposition of ECM proteins in a growing cell-population.
