ABSTRACT
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.
Subject(s)
Membrane Lipids , Phosphatidylinositols , Phosphatidylinositols/metabolism , Cell Membrane/metabolism , Membrane Lipids/metabolism , Cholesterol/chemistry , Biophysics , Lipid Bilayers/chemistry , Phosphatidylinositol 4,5-Diphosphate/analysis , Phosphatidylinositol 4,5-Diphosphate/chemistry , Phosphatidylinositol 4,5-Diphosphate/metabolismABSTRACT
Biomembrane order, dynamics, and other essential physicochemical parameters are controlled by cholesterol, a major component of mammalian cell membranes. Although cholesterol is well known to exhibit a condensing effect on fluid lipid membranes, the extent of stiffening that occurs with different degrees of lipid acyl chain unsaturation remains an enigma. In this review, we show that cholesterol locally increases the bending rigidity of both unsaturated and saturated lipid membranes, suggesting there may be a length-scale dependence of the bending modulus. We review our published data that address the origin of the mechanical effects of cholesterol on unsaturated and polyunsaturated lipid membranes and their role in biomembrane functions. Through a combination of solid-state deuterium NMR spectroscopy and neutron spin-echo spectroscopy, we show that changes in molecular packing cause the universal effects of cholesterol on the membrane bending rigidity. Our findings have broad implications for the role of cholesterol in lipid-protein interactions as well as raft-like mixtures, drug delivery applications, and the effects of antimicrobial peptides on lipid membranes.
