Keith Hayes is a rising senior at Alabama State University, majoring in Biomedical Engineering. He is working in Dr. Guy Genin’s lab, studying mechanical testing of rotator cuff design to reduce surgical failures, and imaging of collagen interactions with fibroblasts.
Fibroblast remodel collagen in three-dimensional matrix
The mechanism by which cells remodel their microenvironment are critical to the mechanobiology of development and wound healing. Although these interactions have been studied extensively in two-dimensional (2D) microenvironments, little is known about them in three dimensional (3D) microenvironments. Here, we identified the mechanism by which fibroblasts interact with their 3D collagen matrices and showed that fibroblast protrusions assist with the efficiency of remodeling and tension generation at the early stages of cell-matrix interactions. While the protrusion tips compressed the matrix, laterally they retracted the matrix to accumulate collagen, generated tension, and reduced the energy needed to retract cell protrusions. Using experimental strain mapping with computational theoretical model, we quantified the mechanical tension generated by fibroblast protrusions and found that actin microfilaments and microtubules are necessary for the generation of tension at the early stages of cell-matrix interactions. We showed that as tension increases at the cell-matrix interface, microtubules in cell protrusions experienced higher compressive forces, which in turn prevented them from growing in length and number. Along with these observations, inhibiting the generation of tension at the early stages of cell-matrix interaction leads to the formation of microtubule-rich thin and long protrusions. Taken together, our results could be used to develop treatment for fibrosis or cirrhosis, that create an abundance of fibrotic tissue.