Elucidating the role of matrix stiffness
Using this system, we demonstrate that normal lung promotes fibroblast motility and polarization, while fibrotic lung immobilizes the fibroblast and promotes myofibroblast differentiation.These context-specific phenotypes are surprisingly both mediated by myosin II.Pro-fibrotic mesenchymal cells are known to be the key effector cells of fibroproliferative disease, but the specific matrix signals and the induced cellular responses that drive the fibrogenic phenotype remain to be elucidated.The key mediators of the fibroblast fibrogenic phenotype were characterized using a novel assay system that measures fibroblast behavior in response to actual normal and fibrotic lung tissue.My diet evolves constantly, due to my constant tweaking and self-experimentation.
Moreover, loss of myosin II activity has opposing effects on protrusive activity in fibroblasts on normal and fibrotic lung.
One area in which 3D models are underrepresented but where they can have an immediate impact is the development of platforms for toxicology screening.
Such models have the potential to address the growing concerns about drug failures in clinical trials due to lack of efficacy or unexpected side effects.
A major challenge of tissue engineering is to build three-dimensional (3D) in vitro models for studying tissue physiology and pathology.
3D in vitro models are the bridge between conventional two-dimensional (2D) tissue culture, which does not capture the complexity of human tissue, and animal models, which are costly, time consuming and raise ethical concerns.
Our earlier studies have also shown that exposing endothelial cells to oxidized modification of low-density lipoproteins (ox LDL) increases endothelial stiffness and facilitates their ability to form cellular networks, suggesting that it facilitates endothelial angiogenic potential.