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

• Published in: Advances in experimental medicine and biology Vol. 1422; p. 61
• Main Authors: Doole, Fathima T, Gupta, Sudipta, Kumarage, Teshani, Ashkar, Rana, Brown, Michael F
• Format: Journal Article
• Language: English
• Published: United States 2023
• Subjects: Biophysics; Cell Membrane - metabolism; Cholesterol - chemistry; Lipid Bilayers - chemistry; Membrane Lipids - metabolism; Phosphatidylinositol 4,5-Diphosphate - analysis; Phosphatidylinositol 4,5-Diphosphate - chemistry; Phosphatidylinositol 4,5-Diphosphate - metabolism; Phosphatidylinositols - metabolism; Membrane viscosity; Area per lipid; Membrane elasticity; Polymer brush model; Solid-state 2H NMR; Neutron spin-echo; Cholesterol; PIP2
• ISSN: 0065-2598
• DOI: 10.1007/978-3-031-21547-6_2

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 ( H 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.