Self-Assembly of Protein Fibrils in Microgravity (2018)

Abstract 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 β -sheet structure. This paper reports the results 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 a model protein that has been shown to replicate the aggregation processes of other amyloid proteins. Here the design and performance of the experimental hardware is described in detail. The flight experiment was carried to the ISS in the Dragon capsule of the SpaceX CRS-5 mission and returned to Earth after 32 days. The lysozyme fibrils formed in microgravity aboard the ISS show a distinctly different morphology compared to fibrils formed in the ground-control (G-C) experiment. The fibrils formed in microgravity are shorter, straighter, and thicker than those formed in the laboratory G-C experiment. For two incubation periods, (2) about 8.5 days and (3) about 14.5 days, the average ISS and G-C fibril diameters are respectively: <m:math xmlns:m="http://www.w3.org/1998/Math/MathML"> <m:mrow> <m:mtable> <m:mtr> <m:mtd> <m:mrow> <m:mi>Period</m:mi> <m:mo> </m:mo> <m:mn>2</m:mn> </m:mrow> </m:mtd> <m:mtd/> <m:mtd> <m:mrow> <m:msub> <m:mi>D</m:mi> <m:mrow> <m:mi>ISS</m:mi> </m:mrow> </m:msub> <m:mo>=</m:mo> <m:mn>7.5</m:mn> <m:mtext>nm</m:mtext> <m:mo>±</m:mo> <m:mn>31</m:mn> <m:mo>%</m:mo> <m:mo>,</m:mo> </m:mrow> </m:mtd> </m:mtr> <m:mtr> <m:mtd/> <m:mtd> <m:mrow> <m:mtext>and</m:mtext> </m:mrow> </m:mtd> <m:mtd> <m:mrow> <m:msub> <m:mi>D</m:mi> <m:mrow> <m:mi>G</m:mi> <m:mo>‐</m:mo> <m:mi>C</m:mi> </m:mrow> </m:msub> <m:mo>=</m:mo> <m:mn>3.4</m:mn> <m:mtext>nm</m:mtext> <m:mo>±</m:mo> <m:mn>31</m:mn> <m:mo>%</m:mo> </m:mrow> </m:mtd> </m:mtr> <m:mtr> <m:mtd> <m:mrow> <m:mi>Period</m:mi> <m:mo> </m:mo> <m:mn>3</m:mn> </m:mrow> </m:mtd> <m:mtd/> <m:mtd> <m:mrow> <m:msub> <m:mi>D</m:mi> <m:mrow> <m:mi>ISS</m:mi> </m:mrow> </m:msub> <m:mo>=</m:mo> <m:mn>6.2</m:mn> <m:mtext>nm</m:mtext> <m:mo>±</m:mo> <m:mn>33</m:mn> <m:mo>%</m:mo> <m:mo>,</m:mo> </m:mrow> </m:mtd> </m:mtr> <m:mtr> <m:mtd/> <m:mtd> <m:mrow> <m:mtext>and</m:mtext> </m:mrow> </m:mtd> <m:mtd> <m:mrow> <m:msub> <m:mi>D</m:mi> <m:mrow> <m:mi>G</m:mi> <m:mo>‐</m:mo> <m:mi>C</m:mi> </m:mrow> </m:msub> <m:mo>=</m:mo> <m:mn>3.6</m:mn> <m:mtext>nm</m:mtext> <m:mo>±</m:mo> <m:mn>33</m:mn> <m:mo>%</m:mo> <m:mo>.</m:mo> </m:mrow> </m:mtd> </m:mtr> </m:mtable> </m:mrow> </m:math> \matrix{{Period\,2} \hfill &#x00026; {} \hfill &#x00026; {{D_{ISS}} = 7.5{\rm{nm}} \pm 31\% ,} \hfill \cr {} \hfill &#x00026; {\rm and} \hfill &#x00026; {{D_{G - C}} = 3.4{\rm{nm}} \pm 31\%} \hfill \cr {Period\,3} \hfill &#x00026; {} \hfill &#x00026; {{D_{ISS}} = 6.2{\rm{nm}} \pm 33\% ,} \hfill \cr {} \hfill &#x00026; {\rm and} \hfill &#x00026; {{D_{G - C}} = 3.6{\rm{nm}} \pm 33\% .}}