Research



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 publication here.
* We were invited to write a comprehensive review on the role of fibronectin mechanobiology in tumorigenesis - See our review article here.
We recently demonstrated a synergy between fibronectin and collagen matrices in tumor development - See our latest publication here.


Tumor ECM mechanobiology
Figure: 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 most recent publication here.


3D conductive scaffolds to control adsorbed ECM proteins conformation
Figure: By engineering 3D platforms that mimic the multiscale physical properties and composition of the tumor microenvironment, we investigate tumor growth and vascularization in highly controlled and tunable conditions.




III - 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 

Figure: 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



IV - 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 demonstrated that fibronectin, which is present in the superficial zone of articular cartilage, enhances the lubrication and wear protection of lubricin during shearSee our Biomacromolecules publication here.

* We also recently showed the synergistic interactions of a synthetic lubricin mimetic with fibronectin for enhanced wear protection. See our most recent publication here.


Biolubrication by lubricin and lubricin-mimicking polymers
Figure: By engineering lubricin-mimicking polymers, we investigate the roles of various synovial fluid components in lubrication and joint protection



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