The structural integrity of tissues depends on the mechanical properties of the extracellular matrix (ECM) network. The shear topology of Fibronectin (FN) contributes to the mechanical durability of the ECM; however, the molecular mechanism accounting for FN elasticity is not well understood. We are investigating the influence of the protein structure on the bulk mechanical properties of a FN network.
In Prof. Parker group FN networks in the form of nanometer thick fabrics were built by releasing micropatterned FN from a thermosensitive substrate. Raman Spectroscopy and fluorescence resonance energy transfer (FRET) confirmed that the conformation of the micropatterned FN changes from an extended to compact conformation within the network upon release from the substrate. When these FN fabrics were uniaxially loaded, they deformed elastically if stretched less than two times their original length. Beyond this threshold, they exhibited plastic deformation.
A computational model based on the eight chain network was developed in my group. The model revealed that the elastic to plastic transition corresponded to the onset of beta-sheet unfolding within the FN III domains. Our results suggest that the elastic properties of FN primarily depends upon the conformational changes of the protein and that domain unfolding initiates plastic deformation. Together, these data suggest that conformational unfolding of the FN endows it with elastic properties and that domain unfolding potentiates plastic deformation of the fabrics.
Mechanical characterization of nanoFabrics using uniaxial tensile testing. (A) Incorporating the eight-chain model to describe FN network mechanics. Before being stretched, the representative volume element (RVE) of the relaxed FN fiber is modeled as a cube with eight chains connected at the center. Extended fibers are stretched, and the RVE is a cuboid. When the stretching force is large enough, beta-sheets within FNIII domains begin to unfold (represented in orange). (B) DIC images of fabrics suspended at two ends by the calibrated microneedles. Deflection (dy) represents load applied during extension. Scale bar is 50 um. (C) Stress-stretch curves for a nanoFabrics. The eight-chain model (red solid line) is fit to the experimental data.
- L.F. Deravi, T. Su, J.A. Paten, J.W. Ruberti, K. Bertoldi, and K.K. Parker. Differential Contributions of Conformation Extension and Domain Unfolding to Properties of Fibronectin Nanotextiles. NanoLetters, 12: 5587–5592, 2012.