ABSTRACT
The plasma membrane (PM) is a quasi-two-dimensional barrier surrounding the cell, providing a controlled environment for the function of its organelles. When the landmark uid mosaic model was proposed in 1972, membrane lipids were pictured as a passive and uid “sea” of nondescript molecules, the uniform matrix in which the more interesting transmembrane and peripheral proteins diffuse and interact (Singer and Nicolson 1972). Over the next four decades, this picture has undergone radical transformations that continue to this day. It is now clear that lateral heterogeneities in the PM arising from nonrandom mixing of lipids and proteins are important in many cellular processes, though the mechanisms governing their formation and dissolution are still not completely understood. These self-organized domains could compartmentalize the bilayer, controlling
8.1 Introduction .......................................................................................................................... 143 8.2 Experimental Tools for Studying Domains in Model Membranes ....................................... 145
8.2.1 Methods to Interrogate Phase Behavior of Multicomponent Model Membranes .... 146 8.2.1.1 Nanoscopic Regime (1-10 nm) .................................................................. 146 8.2.1.2 Mesoscopic Regime (10-200 nm).............................................................. 147 8.2.1.3 “Macroscopic” Regime (>200 nm) ............................................................ 148 8.2.1.4 Assessing the Inuence of Probe Molecules on Bilayer Properties .......... 148 8.2.1.5 Probe-Free Methods .................................................................................. 149
8.2.2 Methods to Determine Tielines in Ternary Mixtures .............................................. 149 8.2.3 Methods to Determine Domain Size ........................................................................ 150
8.2.3.1 Use of FRET to Determine Domain Size .................................................. 151 8.2.3.2 Use of SANS to Determine Domain Size .................................................. 152
8.3 Phase Diagrams of Biomimetic Mixtures ............................................................................ 154 8.3.1 Type II Ternary Mixtures: Micron-Sized Liquid Domains ...................................... 154 8.3.2 Type I Ternary Mixtures: Nanometer-Sized Liquid Domains ................................. 155 8.3.3 Type IIM Behavior: Modulated Phases in a Four-Component Mixture .................... 156
8.4 Toward a Better Raft Model: Insights from the Type IIM Domain Size Transition .............. 158 8.4.1 Modulated Phase Patterns Result from Competing Interactions .............................. 158 8.4.2 Domain Size Depends on Phase Thickness Mismatch in the Nanoscopic Regime .....159
8.5 Moving Forward ................................................................................................................... 160 References ...................................................................................................................................... 161
diffusion and local concentrations of membrane-associated proteins that sort preferentially between different compartments.
