The long-term goal of this project is to improve understanding of how mechanical variability at the nano- and micro-scale affects macroscale properties of tissues. In pursuit of this goal, this project seeks to use clustering and machine vision algorithms to build mechanical models of vascular smooth muscle cell constructs with tunable levels of geometric complexity. Validation of the models uses a combination of traditional soft tissue mechanical testing with novel methods that utilize ink-jet printing and concurrent probe and optical microscopy to assess dynamic structural and mechanical properties of cells living inside 3D-cultures. These tunable models can then be used to assess the level of structural detail that is required for accurate prediction of biomechanical behavior observed in specific sets of experimental conditions.
The long-term educational goal of this project is to increase South Carolina student and parent awareness of the applications and benefits of skills in engineering and computation and thereby, increase the number of students who choose engineering as a career. For this proposal, her educational objectives are: 1) to involve high school, undergraduate, and graduate students directly in the research activities, 2) to increase the number of students from underrepresented groups in the PI's research lab, and 3) to develop new workshops and videos designed to increase SC student and parent enthusiasm for engineering careers by highlighting the broad societal impact of engineering and computation. Meeting these objectives will include leading an interdisciplinary "Creative Inquiry" team of undergraduates, who will develop workshops and video vignettes for South Carolina students. Students from underrepresented groups will be recruited to the team through established campus minority recruitment programs.
Intellectual Merit: This study addresses one of the grand challenges of biomedical research: how to create and assess in vitro cell cultures that accurately reflect in vivo cell responses. Success here will require overcoming numerous technical challenges in machine vision, experimental design, and mechanical modeling and in the fusion of these domains. To assess mechanical properties of cells inside 3D cultures in response to different stimuli, we will adapt a new and novel technique, band excitation atomic force microscopy (BE-AFM), for use in fluids with living cells. By overcoming several of the obstacles the field now faces in characterizing the biomechanics of 3D cell cultures, these studies will result in better characterization of the mechanical properties of vascular smooth muscle cells than has been accomplished to date. The novel methods proposed here are expected to advance the state of the art in modeling of biological tissues. The results can be used to assess the level of biological structural complexity that is required for accurate prediction of mechanical behavior, a necessary step for any multiscale cell-to-organ modeling strategy. By quantifying the effect of structural detail on living cell and tissue mechanical properties in 3D cultures, these studies will bridge the knowledge gap between actual cell and tissue structure and the simplified mechanics models currently used to describe them.
Broader Impact: As medicine shifts focus from macroscale treatments to molecular- and cellular-based therapies, this work will help guide future medical treatment by enabling researchers to better assess how these new types of therapies may influence large-scale tissue function. The BE-AFM and confocal microscopy technique that we will develop to assess the mechanical properties of cells inside thin 3D cultures will enable researchers in a broad range of fields to answer numerous questions beyond those tackled in this proposal. The research plan directly involves graduate, undergraduate, and high-school students. The planned outreach workshops, videos, and curriculum activities will help SC students and parents become more aware of the applications and benefits of skills in computation and engineering. The PI meets year-round with directors of campus programs that support recruitment and retention of minority students and women. Her commitment to providing research opportunities for these students is the foundation of her integrated research and education plan.
