Dr. Sarah Calve

The influence of mechanical loading on the ECM at developing tissue interfaces

ABSTRACT:

Despite decades of work, there has been little success in engineering scaffolds that can successfully restore functionality to damaged musculoskeletal tissues.  What is rarely taken into consideration in scaffold design is that tissues undergo extensive extracellular matrix (ECM) remodeling during development, which is thought to play a significant role in directing cellular behavior in the formation of functional tissue.  Researchers have been unable to capitalize on these instructive cues due to the limited knowledge regarding the material properties of developing musculoskeletal tissues.  In this talk, I will describe how my laboratory has been addressing this gap by developing tools that can measure the composition, turnover, organization and mechanical properties of the ECM in embryonic tissues.  We are combining mass spectrometry and bioorthogonal labeling strategies to identify newly synthesized ECM proteins in the developing mouse.  To determine the organization of these components, we are using confocal microscopy and novel decellularization and clearing protocols to visualize the 3D architecture of ECM networks in the developing limb.  In addition, we created new uniaxial tensile testing methods to visualize train and measure how changes in composition and organization influence the mechanical properties of tissues and ECM networks at the mesoscale.  I will conclude by describing how these techniques can resolve differences in material properties during myotendinous junction formation.