Self-propelled particle modeling, characterization, and imaging of superdiﬀusive mouse ﬁbroblast cells on 2D shape memory polymer substrates
Date of Award
Doctor of Philosophy (PhD)
James H. Henderson
Physical Sciences and Mathematics
Most important biological processes involve cell motion; breast carcinoma cells metastasize throughout a body, epithelial cells spread to close a wound, T-cells rush to ﬁll their immune response duties. The list of essential phenomena is nearly endless, as is the corresponding number of biochemical signaling pathways and other biological features that mediate cell-cell and cell-environment interactions. Understanding these phenomena through the characterization of genetics and biological signaling is a fruitful, bottom-up approach. A complementary approach uses tools from condensed matter and statistical physics to quantify and make predictions about cells and interactions between them. For example, statistical metrics such as mean-squared displacement or velocity auto-correlation functions help characterize the behavior of cell populations with no knowledge of their speciﬁc biochemical interactions. We used these tools to determine the mechanism behind superdiﬀusivity in mouse ﬁbroblast cells. The work put forth in this thesis shows that a generalized heterogeneous self-propelled particle model captures mouse ﬁbroblast trajectory dynamics by replacing parameters in simulations (speed, rotational diﬀusion, tumble frequency) with appropriate distributions. Additionally, in order to quantify the intracellular orientation of mouse ﬁbroblast cells, I developed robust imaging software which identiﬁes and tracks Golgi bodies. When paired with the appropriate and already tracked nucleus, this yields a deﬁnition of cell orientation. After automating this software, we characterized the mechanoresponse of mouse ﬁbroblast cells on static and active 2D shape memory polymer substrates. While the direction of cell nuclei elongation became more aligned after the shape memory polymer substrates were triggered to form wrinkles, as seen previously, the orientation deﬁned by the Golgi body-nucleus axis aligned with the future wrinkle direction even before visible wrinkles were triggered, suggesting intracellular orientation is more sensitive to the environment than previously thought. In summary, this body of work represents novel investigations into the dynamics of mouse ﬁbroblast cells in 2D as well as software contributions for imaging irregular objects in biological data.
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Passucci, Giuseppe, "Self-propelled particle modeling, characterization, and imaging of
superdiﬀusive mouse ﬁbroblast cells on 2D shape memory polymer
substrates" (2018). Dissertations - ALL. 869.