Interview with Dr. Delphine Gourdon and the use of physics to fight cancer and osteoarthritis.
I - Mechanobiology of extracellular matrix proteins in breast cancer
By combining a set of physical science tools with cancer biology our group (i) characterizes the composition, structure, and mechanical properties of tumorous tissues, and (ii) correlates those properties with tumor growth, vascularization, and metastasis. More specifically, we focus on the physical characterization at the molecular, fiber, and cellular scales of extracellular matrix (ECM) proteins (such as fibronectin and collagen) and their interactions with cells, using the integration of intramolecular fluorescence resonance energy transfer (FRET) with the Surface Forces Apparatus (SFA).
* We published the first direct correlation between stiffening and unfolding of the fibronectin matrix - See our Biomaterials publication here.
* We were invited to write a comprehensive review on the role of fibronectin mechanobiology in tumorigenesis - See our CMB Review Article here.
* We established a direct relationship between obesity and breast cancer - See our Science Translational Medicine publication here.
Tumor ECM mechanobiology
By integrating Förster Resonance Energy Transfer (FRET) and the Surface forces Apparatus (SFA) we correlate conformation and mechanics of key proteins from the tumor microenvironment.
II – Design and engineering of 3D scaffolds for cancer research
In collaboration with the Malliaras group at the Ecole des Mines de Saint Etienne we have also succeeded in the fabrication of 3D conducting ECM-mimicking scaffolds made from PEDOT:PSS via an ice-templating method. These scaffolds offer tunable pore size, morphology and stiffness. When a potential is applied to the scaffolds, reversible changes take place in their electrical doping state, which enables precise control over the conformation of adsorbed ECM proteins such as fibronectin. See our JMCB publication here.
3D conductive scaffolds to control adsorbed ECM proteins conformation
By engineering 3D ECM-mimicking platforms that replicate the multiscale physical properties and composition of the tumor microenvironment, we investigate tumor growth and vascularization in highly controlled and tunable conditions.
III - Biolubrication
By combining the Atomic Force Microscope (AFM), the Surface Forces Apparatus (SFA) and a home-made strain device, our group engineers and/or characterizes synthetic and natural biopolymers nano-films for adhesion, protection, lubrication, and various biomedical applications.
* We showed that fibronectin, which is present in the superficial zone of articular cartilage, enhances the lubrication and wear protection of lubricin during shear. See our Biomacromolecules publication here.
* We demonstrated the synergistic interactions of a synthetic lubricin mimetic with fibronectin for enhanced wear protection. See our publication here.
* In collaboration with Dr. Dave Putnam at Cornell, we created and tested a diblock copolymer mimicking lubricin that reduces the coefficient of friction on cartilage to a level equivalent to native lubricin. See our PNAS 2019 paper here.
* We demonstrated that synovial fluid forms long-lived aggregates under shear and that albumin is a key protein mediating such aggregation. See our Langmuir 2019 paper here.
Biolubrication by lubricin and/or lubricin-mimicking polymers
By engineering lubricin-mimicking polymers, we investigate the roles of various synovial fluid components in lubrication and joint protection
IV - Mechanical and structural signature of inflammation
In this project, we elucidate (i) the functional relationships between the structural and mechanical properties of inflamed tissues, and (ii) their impact on the formation of micro-calcifications as they develop, for example during cancer. We focus on the nanoscale materials properties of hydroxyapatite (HAP, closely related to bone mineral), which have been implicated in breast cancer metastasis to bone. More specifically, we seek to understand whether HAP materials properties alter the mineral/organic interface in bone, in particular, the deposition of adsorbed fibronectin, a major extracellular matrix protein.
* We demonstrated that both crystallinity and surface potential of HAP affect the amount and conformation of adsorbed fibronectin. See our publication here.
* We recently showed that the protein-crystal interface mediates adhesion and proangiogenic secretion of various cell types. See our most recent work here.
Effect of altered ECM on inflammation
Nanoscale properties of hydroxyapatite crystals are able to modulate the conformation and composition of deposited ECM, which in turn affect various cell functions among which VEGF and IL-8 secretions