THE EFFECTS OF TERRESTRIAL AND EXTRATERRESTRIAL MECHANOSIGNALING ON CELLULAR AND TISSUE PROCESSES

Abstract

Mechanobiological cues influence biological structures across all scales, from a single cell to a full body. These cues are vital for normal biological processes, such as cell migration and division, tissue structural composition, or astronaut orthostatic intolerance upon return to normal gravity. These cues also influence disease pathogenesis and progression, such as in cancer. Here, I will investigate mechanical influences on biological processes first at a single cell level, where we investigate force dynamics as a glioblastoma cell migrates and invades its surroundings. This investigation has impacts on high grade glioma invasion through the secondary structures of Scherer in the brain. This is a cancer type that has stubbornly resisted many treatment efforts and remains among the most lethal cancers with a 5-year survival of less than 10%. Next, we change scales to the tissue scale, where we investigate the effects of spaceflight on human engineered heart tissues. Spaceflight is well known to result in cardiovascular remodeling. This can have lethal consequences: the only astronauts to have left low Earth orbit are 5 times as likely to die of cardiovascular disease than the rest of the astronaut population. I show that spaceflight has negative consequences on engineered cardiac tissues, which may result from oxidative stress and mitochondrial dysfunction. Finally, both the spaceflight and cancer studies utilize polymeric substrates which are known to absorb drug compounds, preventing accurate drug screenings. We address this problem by showing that a polydimethylsiloxane-polyethylene glycol block copolymer can prevent drug absorption in engineered tissue systems, enabling future studies to conduct accurate drug screenings on the mechanobiological phenomena studied here. Together, this work has impacts on cancer migration, spaceflight, and microphysiological systems in general