Biophysics of Membrane Stiffening by Cholesterol and Phosphatidylinositol 4,5-bisphosphate (PIP2)

Cell membranes regulate a wide range of phenomena that are implicated in key cellular functions. Cholesterol, a critical component of eukaryotic cell membranes, is responsible for cellular organization, membrane elasticity, and other critical physicochemical parameters. Besides cholesterol, other lipid components such as phosphatidylinositol 4,5-bisphosphate (PIP2) are found in minor concentrations in cell membranes yet can also play a major regulatory role in various cell functions. In this chapter, we describe how solid-state deuterium nuclear magnetic resonance (²H NMR) spectroscopy together with neutron spin-echo (NSE) spectroscopy can inform synergetic changes to lipid molecular packing due to cholesterol and PIP2 that modulate the bending rigidity of lipid membranes. Fundamental structure-property relations of molecular self-assembly are illuminated and point toward a length and time-scale dependence of cell membrane mechanics, with significant implications for biological activity and membrane lipid-protein interactions.