Towards an Understanding of the Temperature/ Pressure Configurational and Free-Energy Landscape of Biomolecules

Abstract

Besides temperature, we used hydrostatic pressure as a physical parameter for studying the stability and energetics of biomolecular systems. High pressure is also an important feature of certain natural environments, and the high-pressure phase behaviour of biomolecules is of increasing biotechnological interest. By using thermodynamic, spectroscopic, and scattering techniques, the temperature and pressure-dependent structure and phase behaviour of model biomembrane systems and proteins have been studied. The results demonstrate that combined temperature–pressure-dependent studies can help delineate the conformational and free-energy landscape of biomolecules and hence help to elucidate which features and thermodynamic parameters are essential in determining their stability. Moreover, we present data on the effect of various types of cosolvents on the temperature- and pressure-dependent structure and stability of proteins. We also introduce pressure as a kinetic variable. Applying the pressure-jump relaxation technique in combination with time-resolved synchrotron X-ray diffraction and spectroscopic techniques, the kinetics of lipid phase transitions and un/refolding reactions of proteins have been studied. Finally, recent advances in using the pressure axis for studying misfolding, aggregation, and amyloid fibril formation of proteins and its potential biotechnological and biomedical relevance will be discussed. We conclude with an outlook of the perspectives of high pressure research.