Phosphatidylserine is normally restricted to the inner face where it confers a negative charge and is involved in electrostatic interactions with proteins; however, when it flips to the extracellular face, which happens in cells undergoing apoptosis (programmed cell death), it becomes an “eat me” signal for phagocytes. In the special case of platelets, it serves as a cofactor in the clotting of blood.
• Glycolipids and sphingomyelin are preferentially expressed on the extracellular face; glycolipids (and particularly gangliosides, with complex sugar linkages and terminal sialic acids that confer negative charges) are important in cell–cell and cell–matrix interactions, including inflammatory cell recruitment and sperm–egg interactions.
Certain membrane components associate laterally with each other in the bilayer, leading to distinct domains called lipid rafts. Because inserted membrane proteins have different intrinsic solubilities in various lipid domains, they tend to accumulate in certain regions of the membrane (e.g., rafts) and to become depleted from others. Such nonrandom distributions of lipids and membrane proteins impact cell–cell and cell–matrix interactions, as well as intracellular signaling and the generation of specialized membrane regions involved in secretory or endocytic pathways.
The plasma membrane is liberally studded with a variety of proteins and glycoproteins involved in (1) ion and metabolite transport, (2) fluid-phase and receptor-mediated uptake of macromolecules, and (3) cell–ligand, cell–matrix, and cell–cell interactions. Proteins interact with the lipid bilayer by one of four general arrangements (
Fig. 1.7B • Most proteins are transmembrane (integral) proteins, having one or more relatively hydrophobic α-helical