Cells in a multicellular tissue interact with neighboring cells and the surrounding extracellular matrix to maintain normal tissue properties. Matrix functionalized atomic force microscope (AFM) tips were used to study integrin-matrix adhesions and to induce mechanical stimulation of live cells. Fluorescence imaging experiments performed in combination with AFM studies allow the investigation of the role and molecular interactions between sub-cellular structures involved in transducing mechanical signaling and inducing cellular remodeling. Our results show that stressing integrin-matrix bonds induces intracellular biochemical pathways activation that eventually triggers downstream cellular remodeling. Conversely, intracellular induced pre-stress alters cytoskeletal tension and integrin-matrix adhesions. Thus, we were able to analyze the correlations between (i) cytoskeletal tension, actin fibers remodeling and cell stiffness; and (ii) focal adhesions remodeling, protein activation and strength of integrin-matrix bonds. This novel integrative approach followed by quantitative data analysis provides better understanding of the complex process of cellular adaptive response to microenvironment.

From ligand-receptor interaction to whole cell manipulation using atomic force microscopy

243rd National Meeting (2012)

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