Year: 2017
Type: article
Abstract: Transformations of extracellular matrix (ECM) accompany pathological tissue changes, yet how cell-ECM crosstalk drives these processes remains unknown as adequate tools to probe forces or mechanical strains in tissues are lacking. Here, we introduce a new nanoprobe to assess the mechanical strain of fibronectin (Fn) fibers in tissue, based on the bacterial Fn-binding peptide FnBPA5. FnBPA5 exhibits nM binding affinity to relaxed, but not stretched Fn fibers and is shown to exhibit strain-sensitive ECM binding in cell culture in a comparison with an established Fn-FRET probe. Staining of tumor tissue cryosections shows large regions of relaxed Fn fibers and injection of radiolabeled 111In-FnBPA5 in a prostate cancer mouse model reveals specific accumulation of 111In-FnBPA5 in tumor with prolonged retention compared to other organs. The herein presented approach enables to investigate how Fn fiber strain at the tissue level impacts cell signaling and pathological progression in different diseases.
Source: Nature Communications
Language: English
Subfield: Cell Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $6,990
Funders: National Science Foundation, Wyss Center for Bio and Neuroengineering, Agence Nationale de la Recherche, Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, Eidgenössische Technische Hochschule Zürich, Competence Centre for Materials Science and Technology, FP7 Ideas: European Research Council
Awards: Switching the structure-function relationship of proteins by mechanical forces: physiological and technological implications, HOW PERICELLULAR MATRIX ORCHESTRATES THE ANGIOGENIC-TO-FIBROTIC TRANSITION, Mechanotransduction processes, from the cell periphery to the nucleus, in 2D versus 3D microenvironments, The role of heterochrony in response to deep climate change through Permian-Triassic crises, Novel Imaging and Therapeutic Tools in Systemic Sclerosis
OpenAlex ID: W2768627643