The efficacy of standard pulmonary fibrosis therapies vary due to intra- and inter- patient variability and due the absence of specific biomarkers that can characterize the state of a specific fibrotic lung. Given that only some patients respond to a particular treatment and only few drugs have already been approved for pulmonary fibrosis, a new era of personalized, patient-specific treatments has been initiated, the basis of which is the identification of biomarkers that characterize the state of a particular fibrotic tissue. As fibrosis progression is associated with changes in tissue content and structure, and modifications in mechanical properties and in mechano-cellular phenotype, in a complex and not well-understood manner, the field of mechanobiology arise as a very promising asset in this research area. Although novel therapies are emerging they are not supported by proper biomarkers to characterize the state of particular fibrotic tissue so as to predict tissue response to treatment or even to monitor treatment outcome. Classical histopathology techniques and gene expression have been applied towards this direction, but so far cells’ and tissues’ nanomechanical properties are not considered as possible biomarkers. The project proposes to test the hypothesis that Atomic Force Microscopy (AFM) can identify unique and novel NanoMechanical FingerPrints for pulmonary fibrosis that can be used for the characterization of the state of fibrosis (diagnosis), treatment prediction (prognosis) and monitoring. A combination of cutting-edge experimental approaches will be used in single lung cells and lung fibrotic tissues. Firstly, different types of lung cells (i.e., fibroblasts and myofibroblasts) will be used in order to identify in vitro the NanoMechanical properties of each of the cells that play key role in pulmonary fibrosis, as well the influence of key players in pulmonary fibrosis such as transforming growth factor beta (TGF-β) and extracellular matrix (ECM) stiffness. Subsequently, the NanoMechanical FingerPrints that characterize the state of a particular fibrotic tissue will be explored and evaluated as possible biomarker by using murine models of pulmonary fibrosis. Then, the unique Nanomechanical FingerPrints will be studied using biopsies from mice with pulmonary fibrosis receiving treatment with approved pulmonary fibrosis drug. Finally, the capabilities of the techniques and methods to asses NanoMechanical FingerPrints in human tissue biopsy samples will be investigated. Successful completion of the project will reveal the mechanism of different NanoMechanical FingerPrints and will provide the first steps for the establishment of a novel AFM-based NanoMechanical Biomarker for pulmonary fibrosis staging and treatment prediction with the potential to classify individuals to possible responders to a particular treatment, with easy transfer to the clinic as it can be used parallel to standard biopsy procedures.