Discipline: Biological Sciences
Subcategory: Biomedical Engineering
Session: 2
Room: Exhibit Hall A
Keith B. Hayes, Jr. - Alabama State University
The mechanism by which fibroblasts 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 remodel themselves within their 3D collagen matrices and showed that fibroblasts protrusions assist with the efficiency of remodeling and tension generation at the early stages of cell-matrix interactions. While the tips of these protrusions grew and compressed the matrix, the lateral surfaces of the protrusions 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 interaction. We showed that as tension increases at the cell-matrix interface, microtubules in cell protrusions experienced higher compressive forces, which prevented them from growing in length and number. Taken together, our results show that cell protrusions are an essential component for remodeling. Future research involves treating fibroblasts with Nocodazole and Cytochalasin D to inhibit polymerization of actin microfilaments and microtubules, therefore we hypothesize a decrease in tension generation and accumulation of collagen around fibroblasts.
Funder Acknowledgement(s): Funder Acknowledgement(s): I thank G. Genin and D. Shakiba for help in the field. This work was supported by the Center for Engineering MechanoBiology (CEMB), an NSF Science and Technology Center, under grant agreement CMMI: 15-48571.
Faculty Advisor: Delaram Shakiba, dshakiba@wustl.edu
Role: The research I conducted consisted of culturing the cells in their collagen matrix, imaging the fibroblasts under the confocal microscope and taking the images from the microscope and running through out strain mapping program.