Chapter 4 Notes: Plasma Membrane Structure & Function
Required Reading
Karp – Chapter 4
Sections: 4.1 – Intro to the Plasma Membrane, 4.2 – The Chemical Composition of Membranes
Online resources: glossary, flashcards, quizzes, and practice questions
Intro to the Plasma Membrane
The plasma membrane serves as the outer boundary of the cell, defining its extent and separating its internal environment from the external surroundings.
It is a fragile structure, ranging from 5 to 10 nm in thickness, acting as a barrier between the cellular contents and the outside world.
Membranes are too small to be visualized by light microscopes, necessitating the use of electron microscopes for detailed observation.
Electron microscopy reveals two dark-staining layers, which correspond to the inner and outer polar surfaces of the lipid bilayer.
The ultrastructure of membranes is highly conserved across different species, indicating a fundamental design principle.
Biomembranes
Enclose cells and many organelles, creating distinct compartments within eukaryotic cells.
The relative percentages of different membrane types vary significantly among different eukaryotic cells, as exemplified by the comparison between liver hepatocytes and pancreatic exocrine cells.
Includes Plasma membrane, Rough ER membrane, Smooth ER membrane, Golgi apparatus membrane, Mitochondria (Outer & Inner membrane), Nucleus (Inner membrane), Secretory vesicle membrane, Lysosome membrane, Peroxisome membrane, Endosome membrane
Hepatocyte volume = 5000 \mu m^3 compared to Pancreatic exocrine cell volume = 1000 \mu m^3
Total cell membrane areas: Hepatocyte = 110,000 \mu m^2 and Pancreatic exocrine cell = 13,000 \mu m^2
Intro to the Plasma Membrane: History
Early studies suggested that membranes are primarily composed of lipids, based on their solubility characteristics resembling that of oil.
Surface area measurements of red blood cells, when spread over water, indicated a 1:2 ratio, providing early evidence that membranes are organized as lipid bilayers.
Intro to the Lipid Bilayer
The most energetically favorable orientation for polar head groups is facing the aqueous compartments outside of the bilayer, due to their hydrophilic nature.
Lipid bilayers are stabilized by Van der Waals interactions in the fatty acyl chains. These interactions are individually weak, but collectively numerous and contribute significantly to membrane stability.
Ionic and hydrogen bonds form between the polar head groups with each other and with water, further stabilizing the bilayer structure.
The resulting structure exhibits a hydrophilic exterior, facilitating interaction with the aqueous environment, and a hydrophobic interior, providing a barrier to polar molecules.
Biomembrane Composition
Biomembranes are composed of lipids, proteins, and carbohydrates, each playing distinct roles in membrane structure and function.
Membranes are more than just a simple lipid bilayer; proteins are integral components that mediate various functions.
Proteins are present as individual molecules and complexes that penetrate the bilayer and extend into the surrounding aqueous environment, facilitating interactions with both the interior and exterior of the cell.
The fluidity of the lipid bilayer allows membranes to be dynamic structures, where components are mobile and capable of transient interactions, enabling processes such as signaling and transport.
Structural and functional asymmetry exists in both lipid and protein composition between the two leaflets of the bilayer, contributing to specialized functions.
Membrane Components & Functions
Membranes are lipid-protein assemblies held together by noncovalent bonds, allowing for dynamic interactions and flexibility.
Lipid Bilayer:
Acts as a structural backbone, providing the foundation for membrane organization.
Provides a barrier to prevent random movement of materials into and out of the cell, maintaining cellular integrity.
Membrane Proteins:
Carry out specialized functions, including transport, signaling, and enzymatic activities.
Specialized or differentiated cell types exhibit unique properties resulting from the expression of distinct groups of membrane proteins, allowing for tissue-specific functions.
The lipid-to-protein ratio is linked to function and varies depending on:
Type of cellular membrane
Type of organism
Type of cell
Mitochondria: possess a higher protein content to accommodate the machinery required for electron transport.
Myelin sheath: characterized by a higher lipid content, providing electrical insulation for nerve cells.
Functions of Biomembranes
Compartmentalization: Membranes surround cells and organelles, creating distinct compartments that allow different regions of the cell to have specialized activities, optimizing cellular functions.
Scaffold for biochemical activities: Enzyme and signaling complexes are often anchored at membranes, providing a platform for efficient biochemical reactions and signal transduction pathways.
Selective permeability barrier: Membranes are generally impermeable to most molecules without specialized transport proteins, maintaining the appropriate intracellular environment; they contain machinery to transport specific molecules across the membrane, regulating cellular composition.
Respond to external signals: The plasma membrane contains receptors that allow cells to respond to signals from their environment, enabling cell communication and coordinating cellular responses.
Crucial to energy production: Machinery for ATP synthesis is found in the membranes of chloroplasts and mitochondria, highlighting the role of membranes in energy metabolism.
Major Classes of Membrane Lipids
Three major classes:
Phosphoglycerides (glycerolphospholipids): the most abundant class of lipids in most membranes, characterized by a glycerol backbone.
Sphingolipids: derivatives of ceramide, with diverse functions in cell signaling and membrane structure.
Sterols: contribute to membrane fluidity and stability, with cholesterol being the most common example in animal cells.
Phosphoglycerides (glycerolphospholipids) are the most abundant class in most membranes, providing the structural framework for the lipid bilayer.
Phosphoglycerides
Head groups are linked to glycerol via a phosphodiester bond, creating a polar region that interacts with water.
They exhibit a distinct amphipathic character, with fatty acid chains at one end and a polar head group at the other end, allowing them to form bilayers in aqueous solutions.
Phosphatidylinositol (PI)
Plays an important role in signal transduction, serving as a precursor for signaling molecules that regulate various cellular processes.
All phosphoglycerides exhibit amphipathic character, with both hydrophobic and hydrophilic regions.
Sphingolipids
Derivatives from ceramide (sphingosine + a fatty acid), contributing to membrane structure and cell signaling.
Sphingosine is a long-chain amino alcohol, lacking a glycerol backbone, distinguishing them from phosphoglycerides.
Sphingolipids and Phospholipids
Additional groups can be added to the terminal alcohol of sphingolipids, modifying their properties and functions.
Addition of phosphocholine creates sphingomyelin (SM), a common sphingolipid found in animal cell membranes.
Sphingomyelin (SM) plus phosphoglycerides are ALL Phospholipids!
Glycolipids
Sphingolipids can also have single sugars or branched oligosaccharides as head groups, forming glycolipids.
Glycolipids are found exclusively on the non-cytosolic side of the plasma membrane, oriented towards the extracellular environment.
Sugar groups are added in the lumen of the Golgi, which is topologically equivalent to the outside of the cell, ensuring their proper orientation.
Multiple sugars can be added, forming complex structures called gangliosides, creating hundreds of different combinations with diverse functions.
Possible functions of glycolipids:
Protect the plasma membrane against harsh conditions by forming a protective layer on the cell surface.
Charged glycolipids may bind and affect the concentration of ions, influencing membrane potential and cellular signaling.
May be involved in cell-cell adhesion by binding to lectins (carbohydrate-binding proteins) on adjacent cells, facilitating cell-cell interactions.
Fatty Acid Tails
Fatty acid tails can vary in length and degree of saturation, influencing membrane fluidity and properties.
A fatty acid may be fully saturated, lacking double bonds, monounsaturated, containing one double bond, or polyunsaturated, containing multiple double bonds.
Fatty Acid Nomenclature
Two conventions exist for naming fatty acids, based on either systematic or common names.
Most common fatty acids have an even number of carbon atoms, typically ranging from 16 to 22, reflecting their biosynthesis from two-carbon units.
In phospholipids, C-1 usually contains a C16 or C18 saturated fatty acid, providing stability, while C-2 contains a C18 or C20 unsaturated fatty acid, introducing kinks and influencing membrane fluidity.
The position of double bonds is commonly specified using either the delta ($\Delta$) or omega ($\omega$) nomenclature.
Sterols
Sterols contain four fused carbon rings, forming a rigid planar structure that influences membrane fluidity.
Cholesterol is amphipathic due to the presence of a hydroxyl group, allowing it to insert into lipid bilayers.
Lipid Composition of Biological Membranes
Each type of membrane has characteristic lipids (and proteins), reflecting its specialized functions and interactions.
Table 4.1 shows the lipid compositions of some biological membranes, providing a comparative overview of membrane diversity. Includes Human erythrocyte, Human myelin, Beef heart mitochondria, and E. coli. Displays percentages of Phosphatidic acid, Phosphatidylcholine, Phosphatidylethanolamine, phosphatidylglycerol, Phosphatidylserine, Cardiolipin, Sphingomyelin, Glycolipids and Cholesterol.
Membrane Asymmetry
Different membranes (cytoplasmic, ER, etc.) exhibit distinct lipid compositions, reflecting their specialized functions and interactions.
Even distinct leaflets of the same lipid bilayer exhibit different lipid composition, contributing to functional asymmetry.
Lipid bilayers can be thought of as two independent monolayers with different physical and chemical properties, allowing for specialized functions.
SM: sphingomyelin, PC: phosphatidylcholine, PS: phosphatidylserine, PE: phosphatidylethanolamine, PI: phosphatidylinositol, Cl: cholesterol.
Remember the “–” charge of PS, which is important for protein interactions and signaling.
Functional Importance of Membrane Asymmetry
Proteins can bind the cytosolic face where they require the negatively charged PS for activity, facilitating interactions with specific signaling or structural proteins.
When cells undergo apoptosis, PS is rapidly translocated to the extracellular face, signaling neighboring cells to phagocytose the dead cell, triggering the engulfment and removal of apoptotic cells.
PI is phosphorylated in response to extracellular signals and helps recruit intracellular signaling proteins to the cytosolic face of the membrane, initiating signaling cascades and regulating cellular responses.
Glycolipids are always on the extracellular side and can serve as ligand receptors, mediating cell-cell interactions and recognition processes.
Amphipathic Nature of Lipids
When mixed with water, lipids can form different types of aggregates due to their amphipathic nature, including micelles, bilayers, and liposomes.
Amphipathic compounds contain regions that are polar (hydrophilic) and regions that are nonpolar (hydrophobic), allowing them to interact with both aqueous and nonaqueous environments.
Forces Contributing to Phospholipid Bilayer Formation
The tendency of nonpolar molecules or parts of molecules to associate with each other in aqueous solution, minimizing their contact with water.
Water forces hydrophobic groups together because doing so minimizes their disruptive effects on the hydrogen-bonded network, increasing the entropy of the water molecules.
The hydrophobic effect is NOT an attractive force; it is caused by repulsion from water, driving the self-assembly of lipids into ordered structures.
Bilayers are stabilized by:
van der Waals interactions between acyl chains (weak, but there are many), contributing to the overall stability of the bilayer.
Ionic and hydrogen bonds between the polar head groups with each other and with water, further stabilizing the bilayer structure through hydrophilic interactions.
Spontaneous Closure of Phospholipid Bilayer
Lipid bilayers can self-assemble into closed structures, such as vesicles, due to their amphipathic nature and the hydrophobic effect.
In vitro, phospholipids can assemble spontaneously to form fluid-filled spherical vesicles, called liposomes, which are widely used in research and drug delivery.
These structures have proven invaluable in membrane research, as researchers can insert membrane proteins into liposomes to study their function in a controlled environment, simplifying the complexity of natural membranes.
Liposomes are also becoming an important biomedical tool, used for targeted drug delivery and gene therapy.
Dynamic Nature of Membranes
The hydrophobic nature of the hydrocarbon chains means they cannot be exposed to the aqueous environment; thus, membranes are always continuous, unbroken structures (they often form extensive interconnected networks within the cell).
Lipid bilayers are flexible and deformable, allowing cells to change shape and adapt to different environments.
Their shape can change, as occurs during locomotion or cell division, highlighting their dynamic nature.
Learning Objectives
Understand the basic characteristics of biomembranes, including their structure, composition, and functions.
Be familiar with the three basic types of lipids in cell membranes, including phosphoglycerides, sphingolipids, and sterols.
Know the names and characteristics of the common membrane lipids, such as phosphatidylcholine, sphingomyelin, and cholesterol.
Understand what distinguishes a sphingolipid from a phosphoglyceride, including their structural differences and biosynthetic pathways.
Understand membrane asymmetry, including its causes and functional consequences.
Understand why lipids self-assemble into bilayers and why there are no free edges in the cell, emphasizing the role of the hydrophobic effect.