Shearing cells with single elastic micropillars to influence focal adhesion dynamics [Elektronische Ressource] / presented by Patrick Heil

Dissertationsubmitted to theCombined Faculties for the Natural Sciences and for Mathematicsof the Ruperto-Carola University of Heidelberg, Germanyfor the degree ofDoctor of Natural Sciencespresented byPatrick Heil, M. A.born in FuldaOral examination: November 30th, 2007Shearing Cells withSingle Elastic Micropillarsto Influence Focal Adhesion DynamicsReferees:Prof. Dr. Joachim SpatzProf. Dr. Heinz HornerFocal adhesions (FAs) are important adhesion sites between eukaryotic cells and theextracellular matrix: They mediate cell adhesion, spreading and motility. Over the lastdecade it has become evident that FAs are bi-directional mechano-chemical devices: Theybothexertandsensephysicalforcesbyconvertingbiochemicalsignalsintomechanicalforceand vice versa. As such, they represent a highly fascinating interface between physics andbiology.Recently, ithasbeenshownthattheintrinsicforcegeneratedbythecontractilemachin-eryofthecellthatleadstoFAgrowthcanbesubstitutedbyexternalforces. However, theexact mechanism behind FA-mediated mechanosensing remained unclear. This unsolvedquestion has stimulated several competing theories that attempt to model the physicalprinciples governing the force-induced assembly of adhesion plaque proteins.In this thesis, we present a novel, inexpensive method to micromanipulate living cellswith single elastic micropillars and discuss the effect of lateral shear stress on focal adhe-sion dynamics of fibroblasts.