title: Quantitative analysis of 3D extracellular matrix remodelling by pancreatic stellate cells.
abstract: Extracellular matrix (ECM) remodelling is integral to numerous physiological and pathological processes in biology, such as embryogenesis, wound healing, fibrosis and cancer. Until recently, most cellular studies have been conducted on 2D environments where mechanical cues significantly differ from physiologically relevant 3D environments, impacting cellular behaviour and masking the interpretation of cellular function in health and disease. We present an integrated methodology where cell-ECM interactions can be investigated in 3D environments via ECM remodelling. Monitoring and quantification of collagen-I structure in remodelled matrices, through designated algorithms, show that 3D matrices can be used to correlate remodelling with increased ECM stiffness observed in fibrosis. Pancreatic stellate cells (PSCs) are the key effectors of the stromal fibrosis associated to pancreatic cancer. We use PSCs to implement our methodology and demonstrate that PSC matrix remodelling capabilities depend on their contractile machinery and β1 integrin-mediated cell-ECM attachment.
authors.affiliation: Cellular and Molecular Biomechanics Laboratory, Department of Bioengineering, Faculty of Engineering, Imperial College London, South Kensington Campus, London SW7 2AZ, UK.
authors.forename: Benjamin K
authors.initials: BK
authors.lastname: Robinson
authors.affiliation: Cellular and Molecular Biomechanics Laboratory, Department of Bioengineering, Faculty of Engineering, Imperial College London, South Kensington Campus, London SW7 2AZ, UK.
authors.forename: Ernesto
authors.initials: E
authors.lastname: Cortes
authors.affiliation: Cellular and Molecular Biomechanics Laboratory, Department of Bioengineering, Faculty of Engineering, Imperial College London, South Kensington Campus, London SW7 2AZ, UK.
authors.forename: Alistair J
authors.initials: AJ
authors.lastname: Rice
authors.affiliation: Cellular and Molecular Biomechanics Laboratory, Department of Bioengineering, Faculty of Engineering, Imperial College London, South Kensington Campus, London SW7 2AZ, UK.
authors.forename: Muge
authors.initials: M
authors.lastname: Sarper
authors.affiliation: Cellular and Molecular Biomechanics Laboratory, Department of Bioengineering, Faculty of Engineering, Imperial College London, South Kensington Campus, London SW7 2AZ, UK a.del-rio-hernandez@imperial.ac.uk.
authors.forename: Armando
authors.identifier: http://orcid.org/0000-0001-5062-8910
authors.initials: A
authors.lastname: Del Río Hernández
keywords: 3D Biology; AFM; ECM remodelling; SHG