Mechanobiology of the extracellular matrix in breast cancer in 2D and 3D

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

Mechanobiology of the tumor ECM via FRET

Mechanobiology of the tumor ECM via FRET
Collaborators: C. Fischbach (BME, Cornell) and M. Smith (BME, Boston University).

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 –

3D conductive scaffolds to control adsorbed ECM proteins conformation

3D conductive scaffolds to control adsorbed ECM proteins conformation
Collaborators: G. Malliaras (EMSE, France), C. Fischbach (BME, Cornell) and E. Giannelis (MSE, Cornell).
Funding: NSF-CMMI & NIH-NCI.

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 most recent publication here. 

We also recently showed that unfolded fibronectin adsorbed onto nano-rough HAP facets with low surface charge density is associated with elevated proangiogenic and proinflammatory secretions by breast cancer cells. Read more here.

Role of altered ECM materials properties in inflammation

Role of altered ECM materials properties in inflammation
Collaborators: L. Estroff (MSE, Cornell) and C. Fischbach (BME, Cornell).
Funding: NSF-DMR & NIH-NCI.

Biolubrication & Bioadhesion

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 recently demonstrated that fibronectin, which is present in the superficial zone of articular cartilage, mediates enhanced lubrication and wear protection of lubricin during shearSee our most recent biolubrication-associated publication here.

Biolubrication by lubricin and lubricin-mimicking polymers

Role of altered ECM materials properties in inflammation

Bioadhesion by mussel adhesive proteins

Role of altered ECM materials properties in inflammation
Collaborators: J. Israelachvili (ChemE, UCSB), H. Waite (Marine Biol., UCSB), D. Putnam (CBE, Cornell) and L. Bonnassar (BME, Cornell). 
Funding: CCMR (NSF-DMR).