CAREER: Characterization of the Strain Rate-Dependent Mechanical Behavior of the Cell-Cell Adhesion Interface

This Faculty Early Career Development (CAREER) award supports research to characterize the mechanical behavior of single cell-cell adhesions. Cell-cell adhesions integrate cells into tissues. They relay signals between the extracellular environment and cells. They also experience strains of different magnitudes and rates. Currently, there is a lack of understanding about the strain rate-dependent behavior of the cell-cell adhesion. This is particularly true of the response mechanisms at play across the spectrum of strain rates. This knowledge is critical in understanding various pathological conditions and developmental defects where cell-cell adhesions play a significant role. This research project will quantify the stress-strain relationship of a single cell pair. Different tensile strain rates will be used to examine the process that governs the responses of the cell-cell adhesions. The results will elucidate the coordinated response from the cytoskeleton network and cell-cell adhesions. The complementary outreach program will translate laboratory innovations into learning opportunities for young kids. This will be accomplished through interactive educational platforms for K-12 students. This CAREER award will also provide research opportunities for undergraduate students via a laboratory mentoring program. The specific goal of the research is to uncover the mechanisms governing the mechanical response of single cell-cell adhesion junctions when they are subjected to mechanical strains of different strain rates. It is generally accepted that stress accumulation in the cytoskeleton network is strain rate-dependent. Thus, it is critical to understand how stress relaxation by the cytoskeleton under different strain rates coordinates with the enhancement of cell-cell adhesion to prevent fracture of multicellular structures. The central hypothesis being tested is that under tensile loading cytoskeleton reorganization and cell-cell adhesion enhancement/rupture are loading rate-dependent and driven by mechanosensing molecules at the cell-cell adhesion. Two research objectives, focusing on the cytoskeleton and the cell-cell adhesion, respectively, include: 1) examine the rate-dependent stress relaxation and tensioning of the cell adhesion-cytoskeleton network, and 2) examine the rate-dependent enhancement of cell-cell junctions that reduces rupture potential under tensile loads. Through the two objectives, one of the fundamental questions in mechanobiology will be answered: what fundamental mechanical variables do cell-cell adhesions sense and respond to, force/stress or deformation/strain, or the rate change of these variables? The success in completion of the objectives will build a solid foundation for pioneering the study of the strain rate-dependent mechanical behavior of cell-cell adhesions, leveraging the unique capability of a single cell-cell adhesion interrogation platform. 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.