Aaron D. Simmons’s research while affiliated with University of Oklahoma and other places

Cardiovascular mechanical stresses trigger physiological and pathological cellular reactions including secretion of Transforming Growth Factor β1 ubiquitously in a latent form (LTGF-β1). While complex shear stresses can activate LTGF-β1, the mechanisms underlying LTGF-β1 activation remain unclear. We hypothesized that different types of shear stress differentially activate LTGF-β1. We designed a custom-built cone-and-plate device to generate steady shear (SS) forces, which are physiologic, or oscillatory shear (OSS) forces characteristic of pathologic states, by abruptly changing rotation directions. We then measured LTGF-β1 activation in platelet releasates. We modeled and measured flow profile changes between SS and OSS by computational fluid dynamics (CFD) simulations. We found a spike in shear rate during abrupt changes in rotation direction. OSS activated TGF-β1 levels significantly more than SS at all shear rates. OSS altered oxidation of free thiols to form more high molecular weight protein complex(es) than SS, a potential mechanism of shear-dependent LTGF-β1 activation. Increasing viscosity in platelet releasates produced higher shear stress and higher LTGF-β1 activation. OSS-generated active TGF-β1 stimulated higher pSmad2 signaling and endothelial to mesenchymal transition (EndoMT)-related genes PAI-1, collagen, and periostin expression in endothelial cells. Overall, our data suggest variable TGF-β1 activation and signaling occurs with competing blood flow patterns in the vasculature to generate complex shear stress, which activates higher levels of TGF-β1 to drive vascular remodeling.

The mechanical properties of soft materials are critically important for a wide range of applications ranging from packaging to biomedical purposes. We have constructed a simple mechanical testing apparatus using off-the-shelf materials and open-source software for a total cost of less than $100. The device consists of a wooden frame supporting a central loading apparatus attached via drawer slides. To perform a mechanical test, a sample is secured within two custom-made 3D-printed clamps affixed to brackets on the base of the frame and the load cell. The extension force is applied by the user pulling on a rope, moving the central loading apparatus up (thereby stretching the sample) while recording the force (measured by a load cell) and the displacement (measured by an ultrasonic sensor). The load cell and ultrasonic sensor are linked to an Arduino microcontroller connected to a laptop through a USB port for data acquisition and analysis. This instrument was easy to assemble and enabled students to better grasp the meaning of tensile testing while promoting experimentation with electronics, computer programming, and mechanical design. Because of its low cost and ease of use, this Arduino-based uniaxial tensile tester can be an ideal device to introduce the concepts of mechanical properties, among other concepts, to students in numerous fields.