Abstract
Early cell membrane models placed most proteins external to lipid bilayers in trimolecular structures or as modular lipoprotein units. These thermodynamically untenable structures did not allow lipid lateral movements independent of membrane proteins. The Fluid–Mosaic Membrane Model accounted for these and other properties, such as membrane asymmetry, variable lateral mobilities of membrane components and their associations with dynamic complexes. Integral membrane proteins can transform into globular structures that are intercalated to various degrees into a heterogeneous lipid bilayer matrix. This simplified version of cell membrane structure was never proposed as the ultimate biomembrane description, but it provided a basic nanometer scale framework for membrane organization. Subsequently, the structures associated with membranes were considered, including peripheral membrane proteins, and cytoskeletal and extracellular matrix components that restricted lateral mobility. In addition, lipid–lipid and lipid–protein membrane domains, essential for cellular signaling, were proposed and eventually discovered. The presence of specialized membrane domains significantly reduced the extent of the fluid lipid matrix, so membranes have become more mosaic with some fluid areas over time. However, the fluid regions of membranes are very important in lipid transport and exchange. Various lipid globules, droplets, vesicles and other membranes can fuse to incorporate new lipids or expel damaged lipids from membranes, or they can be internalized in endosomes that eventually fuse with other internal vesicles and membranes. They can also be externalized in a reverse process and released as extracellular vesicles and exosomes. In this Special Issue, the use of membrane phospholipids to modify cellular membranes in order to modulate clinically relevant host properties is considered.
Highlights
Cell MembranesCell or plasma membranes are the first cellular barriers encountered by extracellular ions, molecules, lipid vesicles and globules, viruses and other cells [1]
Danielli and Davson [10] proposed that cellular membranes were lipid bilayers, as proposed by Gorter and Grendel [7], that interacted with flattened or beta-sheet proteins via the hydrophilic head groups of membrane phospholipids
The concept that the matrix of cellular membranes contains amphipathic phospholipids that self-assemble to form lipid bilayers due to the energy provided by the hydrophobic effect and van der Waals forces has evolved over the years [3,6,13]
Summary
Cell or plasma membranes are the first cellular barriers encountered by extracellular ions, molecules, lipid vesicles and globules, viruses and other cells [1]. A basic concept in the organization of cellular membranes is that they are made up of amphipathic molecular components that associate into macro-structures that exclude water interactions on their hydrophobic surfaces. The concept that the matrix of cellular membranes contains amphipathic phospholipids that self-assemble to form lipid bilayers due to the energy provided by the hydrophobic effect and van der Waals forces has evolved over the years [3,6,13]. Later, membraneassociated proteins were added that were not generally associated with the hydrophobic matrix of membranes Their transient interactions with membranes occurred through protein or lipid attachments instead of intercalation into a membrane lipid matrix, and their function was mainly to provide connections with other cellular components, such as enzymes, protein complexes, cytoskeletal elements and other components and structural integrity [3,15]. Membrane protein clustering into specific domains appears to involve interactions with lipid domains, electrostatic interactions between proteins and lipids, inner membrane surface protein scaffolding and other properties of membrane constituents (reviewed in [31])
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