Self-Assembly of Protein Fibrils in Microgravity
Deposits of insoluble protein fibrils in human tissue are associated with amyloidosis and neurodegenerative diseases. Different proteins are involved in each disease; all are soluble in their native conformation in vivo, but by molecular self-assembly, they all form insoluble protein fibril deposits with a similar cross -sheet structure. The study of molecular self-assembly is also of interest to origin of life. The development of cellular activity was dependent upon the creation of large complex molecular structures in the chemical and environmental conditions present when life originated. Although life probably arose in a planetary environment, microgravity is known to effect cellular function. This dissertation reports the preparation, results and analysis of an experiment in molecular self-assembly, carried out in microgravity, on the International Space Station (ISS). The Self-Assembly in Biology and the Origin of Life (SABOL) experiment was designed to study the growth of lysozyme fibrils in microgravity. Lysozyme is used as a model protein that has been shown to replicate the aggregation processes of other amyloid proteins. The design and performance of the experimental hardware is described in detail. Based on a 1U NanoLab module, two identical systems were built one for fiight and one for ground-control. The flight experiment was carried to the ISS in the Dragon capsule of the SpaceX CRS-5 mission and returned to Earth in the same Dragon after about 32 days on board the ISS. The lysozyme fibrils formed in microgravity show a distantly different morphology compared to fibrils formed in an identical ground-control experiment. Ground-based protein concentration trials were conducted to mimic some of the effects done on fi bril formation in microgravity. A detailed comparison of the differing initial protein concentrations and how it affected fibril morphology was conducted.