Actin Polymerization and Bundling: Exploring their Temperature and Pressure Limits

Today's living systems are organized in highly dynamic and structured functional units providing a platform for life. Despite the origin of life took place under extreme environmental conditions, few higher organisms can still be found in regions with extreme conditions of pressure and temperature. In vivo experiments revealed that, compared to other cellular components, the temperature and pressure stability of the cytoskeleton is rather limited. Actin, a key protein for cell shape and movement, is highly conserved and the most abundant protein in eukaryotes. Its polymerization reaction is essential to provide driving force for cellular motility and mechanical resistance for cell shape. Upon polymerization, actin filaments (F-actin) can be further organized into different architectures including crosslinked and bundled networks. In this study, using the examples of actin polymerization and bundling we illustrate the importance of actin-binding proteins for maintaining the stability and dynamics of the cytoskeleton in a pressurized world. Using preformed gelsolin-actin nuclei and applying stopped-flow methodology, we quantitatively studied the polymerization process of actin as a function of temperature and pressure and found that the temperature-pressure sensitivity of its kinetics is essentially due to the initial de novo nucleation event rather than the elongation reaction of F-actin, highlighting the need of actin nucleation factors to bypass the energetically costly and pressure-sensitive de novo nucleation in vivo ensuring formation of the microfilament (1). Furthermore, using small-angle X-ray scattering and transmission electron microscopy we compare the temperature-pressure stability of actin bundles formed by the protein fascin and Mg2+ and show that the naturally occurring bundles are more adapted to apply mechanical forces, also under high pressure conditions (2).(1) M. Gao, R. Winter (2015) ChemPhysChem, http://dx.doi.org/10.1002/cphc.201500633.(2) M. Gao, M. Berghaus, ⋯, R. Winter (2015) Angew. Chemie Int. Ed. 54:11088.