Microgravity as an environment for macromolecular crystallization – an outlook in the era of space stations and commercial space flight

ABSTRACT In 2005 we reviewed microgravity for macromolecular crystallization, four years after the final flight of the Space Shuttle Orbiter, and five years before the first commercial flight to the International Space Station. Since then, there have been developments in access to space and advances in technology. More regular space flight is becoming a reality, new diffraction data detectors have become available that have both a faster readout and lower noise, a new generation of extremely bright X-ray sources and X-ray free-electron lasers (XFELs) have become available with beam collimation properties well suited geometrically to more perfect protein crystals. Neutron sources, instrumentation, and methods have also advanced greatly for yielding complete structures at room temperature and radiation damage-free. The larger volumes of protein crystals from microgravity can synergise well with these recent neutron developments. Unfortunately, progress in harnessing these new technologies to maximize the benefits seen in microgravity-grown crystals has been patchy and even disappointing. Despite detailed theoretical analysis and key empirical studies, crystallization in microgravity has not yet produced the results that demonstrate its potential. In this updated review we present some of the key lessons learned and show how processes could yet be optimized given these new developments.