Exploring the temperature-pressure configurational landscape of biomolecules: from lipid membranes to proteins.

Hydrostatic pressure has been used as a physical parameter for studying the stability and energetics of biomolecular systems, such as lipid mesophases and proteins, but also because high pressure is an important feature of certain natural membrane environments and because the high-pressure phase behaviour of biomolecules is of biotechnological interest. By using spectroscopic and scattering techniques, the temperature- and pressure-dependent structure and phase behaviour of lipid systems, differing in chain configuration, headgroup structure and concentration, and proteins have been studied and are discussed. A thermodynamic approach is presented for studying the stability of proteins as a function of both temperature and pressure. The results demonstrate that combined temperature-pressure dependent studies can help delineate the free-energy landscape of proteins and hence help elucidate which features and thermodynamic parameters are essential in determining the stability of the native conformational state 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 un/refolding of proteins has been studied. Finally, recent advances in using pressure for studying misfolding and aggregation of proteins will be discussed.