In order to build healthy tissues and organs, cells need constant biochemical and mechanical feedback from their environment. Several diseases, including tumor growth, are linked to abnormal tissue hardening or softening, a mechanical effect known to either cause or exacerbate the progression of the disease. However, it remains largely unknown how these mechanical effects control tissue growth and the appearance of disease, simply because no methodologies existed to reveal how cells respond to these mechanical cues. The research supported by this Faculty Early Career Development (CAREER) award will overcome these difficulties by using a set of cutting-edge techniques to reveal for the first time the mechanical environment of cells and their response to this environment directly as tissues are being built. Beyond the discovery of new fundamental mechanisms underlying tissue and organ growth, the results of this research will contribute to society by helping in many tissue engineering applications as well as in the understanding and diagnosis of cancer and several other diseases associated with tissue mechanical abnormalities. Moreover, this project will provide many opportunities for underrepresented students to engage in interdisciplinary research projects, thereby promoting engineering education.
Mechanical cues, such as forces or the mechanical properties of the cellular microenvironment, are known to affect the behavior of cells in culture conditions, but it is unknown how these affect cells in living 3D tissues. A key necessary step to approach biomechanics and mechanobiology questions in 3D multicellular systems, especially during the formation of tissues and organs, is being able to quantitatively measure the endogenous mechanical cues in these systems. Using two novel microdroplet-based techniques that enable a direct quantification of spatiotemporal variations in mechanical forces and mechanical properties within developing 3D tissues, the proposed research will reveal the differential mechanical cues that cells perceive during vertebrate body axis elongation, decode the spatial and temporal characteristics of such mechanical cues, and quantify the mechanical response of cells to controlled mechanical stimuli, all within the developing zebrafish embryo.
