CAREER: Liquid Crystallinity as a Tool to Probe Cell and Protein Behavior in Gel Biomaterials

University Of Connecticut, Storrs CT

Investigators

Abstract

Mechanical properties of tissues can influence how individual cells behave. Changes in mechanical properties are often hallmarks of disease and are critical for healthy repair following injury. However, how the cells sense these properties at different length scales and how that information affects cell function are not well-understood. This CAREER research investigates new polymers that are compatible with human cells and can be used to surround cells for laboratory culture in three-dimensional (3D) gels. The polymers are liquid crystalline (LC), which means that they can be designed to order at different length scales. The research will establish new gel materials and determine how protein orders within the gels. The work will then determine how the length scales at which cells sense mechanical properties affect cell function, as well as investigate materials-based approaches to tune protein deposition/organization and cellular activation. The knowledge of cell behavior gained from this CAREER project can help discover and validate therapies for diseases such as fibrosis, a pathology characterized by excess scarring, and can contribute to new materials for regenerative medicine. The educational goal of this project is to provide fifth and sixth grade students, who are vulnerable along gendered lines to decreased self-efficacy in STEM, with opportunities to practice resilience or "grit", a measurable and trainable skill. Research-based activities will allow these students to attempt challenges and confront and overcome failure in a safe environment with support from undergraduate mentors. The integrated educational and research program aims to 1) teach resiliency skills to underserved students to increase attitudes of STEM self-efficacy, 2) train undergraduate and graduate students in research and to communicate research to diverse audiences, and 3) broadly distribute results of that research and generate interest in STEM. Part 2: Technical Summary Analysis of cell cultures in vitro generates knowledge of cell behavior and can reveal therapeutic targets, validate clinical therapies, and establish new materials for regenerative medicine. Mammalian cells alter function in response to culture substrates with different elastic and viscous (viscoelastic) properties, yet how cells sense viscoelasticity is not well understood. Given the heterogeneity of natural tissues, clarifying at what length scales (from microns to millimeters) cells sense and/or respond to viscoelasticity is hypothesized to be a critical design variable unaccounted for in current culture substrates. This project will establish a new class of cytocompatible, three-dimensional (3D) liquid crystalline (LC) gels, to enable encapsulation of cells in vitro and to pioneer new insight into cellular/subcellular responses to local 3D environments. The first objective will synthesize LC hydrogels and establish design parameters that control LC polymer order and material properties. The hydrogels will be combined with Type I collagen and fibroblasts to determine how LC polymer ordering affects the organization of reconstituted and de novo synthesized collagen. The second objective will quantify fibroblast activation and protein responses to changes in the viscoelasticity of the local 3D environment at varying length scales. The educational goal centers on resilience or "grit" as a measurable, trainable skill key to self-efficacy in STEM. A novel service learning model will integrate research with education, focusing on underrepresented students at the late elementary and early middle school level, a time when gender differences in STEM self-efficacy arise and affect both the rate at which students enter and continue with STEM studies. Research-integrated activities will allow 5th and 6th grade students to attempt challenges and confront and overcome failure in a safe environment with support from undergraduate student mentors. The integrated and sustainable educational and research program is expected to 1) teach resiliency skills to underserved students, 2) train undergraduate and graduate students in research and to communicate research to diverse audiences, and 3) broadly disseminate results and generate interest in STEM research. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.