Cells in vivo are often embedded within a fibrous material termed the extracellular matrix that regulates many cellular processes, including stem cell differentiation and cancer progression. Understanding the functions of extracellular matrices has enormous potential for the betterment of human health. However, matrix protein function is often investigated in a context that is not physiological, for example as an adsorbed monolayer on the surface of a Petri dish. Increasing evidence suggests that the native, fibrillar structures have different, and in many cases more dynamic, properties than the individual molecules from which they are made.

This talk will present multidisciplinary efforts which purpose to characterize the properties of fibronectin fibers, a highly extensible fiber present within the extracellular matrix during development and wound healing that displays a number of binding sites for cell adhesion molecules and soluble signaling molecules. First, spectroscopic tools were used to demonstrate that cell traction forces stretch fibronectin fibers and that this mechanical extension is mediated by alterations in molecularconformation. Next, a novel cell-free assay was developed for the generation of fibronectin fibers that could be probed both mechanically and biochemically. This tool was used to demonstrate that fibronectin’s mechanical properties vary markedly as the fibers are stretched and furthermore that mechanical strain alters fibronectin adhesivity for soluble cell signaling molecules. These data indicate that the function of fibronectin fibers can be mechanically actuated. Finally, a modeling approach was developed that permits a multi-scale understanding of the mechanical/biochemical properties of this fibrous matrix structure by linking molecular mechanics with the bulk mechanical properties of the material.

 Dr. Smith is being hosted by BME Associate Professor Tom Barker, thomas.barker@bme.gatech.edu