Objective Force is ubiquitous in nature and physical stimuli are crucial for cell function. How cells process forces determines key physiological processes such as cell growth and differentiation, in which cells divide or differentiate according to the chemical and physical cues cells receive from the extracellular matrix. Physical stimuli have also been involved in the development of pathological processes, especially those in which cells lose the proper physical communication with the environment, such as cancer and metastasis formation. The major components of the mechanotransduction signaling pathways that transmit and translate these physical messages will most likely to be the molecules that directly sense force from the extracellular matrix. These molecules are integrins and the proteins that link them to the cytoskeleton. Here, I propose a multidisciplinary approach aimed to elucidate how force can modulate cellular behaviour. The project will focus on (i) determining how cells sense, produce and interpret forces and (ii) the cellular outcomes resulting from these processes. First, a nanotechnological suite composed of magnetic tweezers, and siRNA technology will be developed and employed to determine the roles of the molecules involved in these mechanical pathways. Second, the molecular mechanisms that trigger the interaction of proteins under force application will be studied. Several biophysical techniques such as magnetic tweezers, Atomic Force Microscopy (AFM), Total Internal Reflection Fluorescence (TIRF), and Fluorescence Resonance Energy Transfer (FRET) will be used here. Finally, a comparative study of the effect of force in normal and malignant cells will be accomplished. It will be tested whether or not these pathways are involved in the expression of genes in the nucleus, and the ability of normal and malignant cells to respond to external forces and to apply forces on their substrates. Magnetic tweezers, and elastic pillars will be used here. Fields of science natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsnatural sciencesphysical sciencesopticsmicroscopymedical and health sciencesclinical medicineoncology Programme(s) FP7-IDEAS-ERC - Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Topic(s) ERC-SG-LS1 - ERC Starting Grant - Molecular and Structural Biology and Biochemistry Call for proposal ERC-2011-StG_20101109 See other projects for this call Funding Scheme ERC-SG - ERC Starting Grant Coordinator IMPERIAL COLLEGE OF SCIENCE TECHNOLOGY AND MEDICINE Address South kensington campus exhibition road SW7 2AZ London United Kingdom See on map Region London Inner London — West Westminster Activity type Higher or Secondary Education Establishments Administrative Contact Shaun Power (Mr.) Principal investigator Armando Emeterio Del Río Hernández (Dr.) Links Contact the organisation Opens in new window Website Opens in new window EU contribution No data Beneficiaries (2) Sort alphabetically Sort by EU Contribution Expand all Collapse all IMPERIAL COLLEGE OF SCIENCE TECHNOLOGY AND MEDICINE United Kingdom EU contribution € 1 841 836,60 Address South kensington campus exhibition road SW7 2AZ London See on map Region London Inner London — West Westminster Activity type Higher or Secondary Education Establishments Administrative Contact Shaun Power (Mr.) Principal investigator Armando Emeterio Del Río Hernández (Dr.) Links Contact the organisation Opens in new window Website Opens in new window Other funding No data QUEEN MARY UNIVERSITY OF LONDON Participation ended United Kingdom EU contribution € 156 494,40 Address 327 mile end road E1 4NS London See on map Region London Inner London — East Tower Hamlets Activity type Higher or Secondary Education Establishments Administrative Contact Greg Dow (Mr.) Links Contact the organisation Opens in new window Website Opens in new window Other funding No data
