Detection of Emergent Mechanical Properties of Biologically Complex Cellular States

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Abstract This is a Diversity Supplement to R01EB024989 for the career development of Taylor Thomsen, a first- generation college student who is entering her 2nd-year of graduate school in the UCSF-UC Berkeley Graduate Program in Bioengineering. Thomsen has just joined the Sohn Research Laboratory for her doctoral thesis. The parent grant application pursues the hypothesis that breast cancer risk factors such as age, genetics, and family history integrate through molecular pathways in human mammary epithelial cells (HMECS), resulting in a unique mechanical age in a woman that is distinct from her chronological age. The disparity in mechanical and chronological age measures the susceptibility of a woman’s risk for breast cancer. Under the parent grant, HMEC mechanical properties will be measured using a combination of planar-flow mechano-node-pore sensing (mechano-NPS) and in silico modeling, and mechanical age will be determined through machine learning. Under this Diversity Supplement, Thomsen will develop a new platform—circular mechano-NPS—that will allow her to investigate the mechanical memory of human mammary epithelial cells (HMECs) as they undergo cyclical mechanical dosing. In Aim 1, she will design and prototype the circular mechano-NPS device and test different prototypes using non-malignant MCF10A cells. In Aim 2, she will perform initial mechanical memory experiments with HMEC strains. Ultimately, Thomsen will explore the differences in the mechanical memory of HMECs among young and old women and women who carry who carry germline BRCA1, BRCA2, or PALB2 variants. Mentoring and career development plans for Thomsen are outlined in this supplement, as well as how Thomsen’s appointment promotes diversity within UC Berkeley and the national STEM community. .