Ultrafast Dynamics at Lipid-Water Interfaces.

Lipid membranes are more than just barriers between cell compartments; they provide molecular environments with a finely tuned balance between hydrophilic and hydrophobic interactions that enable proteins to dynamically fold and self-assemble to regulate biological function. Characterizing dynamics at the lipid-water interface is essential to understanding molecular complexities from the thermodynamics of liquid-liquid phase separation down to picosecond-scale reorganization of interfacial hydrogen-bond networks.Ultrafast vibrational spectroscopy, including two-dimensional infrared (2D IR) and vibrational sum-frequency generation (VSFG) spectroscopies, is a powerful tool to examine picosecond interfacial dynamics. Two-dimensional IR spectroscopy provides a bond-centered view of dynamics with subpicosecond time resolutions, as vibrational frequencies are highly sensitive to the local environment. Recently, 2D IR spectroscopy has been applied to carbonyl and phosphate vibrations intrinsically located at the lipid-water interface. Interface-specific VSFG spectroscopy probes the water vibrational modes directly, accessing H-bond strength and water organization at lipid headgroup positions. Signals in VSFG arise from the interfacial dipole contributions, directly probing headgroup ordering and water orientation to provide a structural view of the interface.In this Account we discuss novel applications of ultrafast spectroscopy to lipid membranes, a field that has experienced significant growth over the past decade. In particular, ultrafast experiments now offer a molecular perspective on increasingly complex membranes. The powerful combination of ultrafast, interface-selective spectroscopy and simulations opens up new routes to understanding multicomponent membranes and their function. This Account highlights key prevailing views that have emerged from recent experiments: (1) Water dynamics at the lipid-water interface are slow compared to those of bulk water as a result of disrupted H-bond networks near the headgroups. (2) Peptides, ions, osmolytes, and cosolvents perturb interfacial dynamics, indicating that dynamics at the interface are affected by bulk solvent dynamics and vice versa. (3) The interfacial environment is generally dictated by the headgroup structure and orientation, but hydrophobic interactions within the acyl chains also modulate interfacial dynamics. Ultrafast spectroscopy has been essential to characterizing the biophysical chemistry of the lipid-water interface; however, challenges remain in interpreting congested spectra as well as designing appropriate model systems to capture the complexity of a membrane environment.