Membrane Structure and function

Section #3 of CBIO3400

  • Instructor: Dr. Heike Kroeger

  • Date: 03/16/2026

  • Topic: Structure and Function of Biological Membranes

Agenda

  • Membrane structure and composition

  • Membrane function

  • FRAP as mechanism to study protein and lipid dynamics

Learning Objectives

Learning Objective #1
  • Membrane structure, composition, and permeability

    • Describe the organization of the lipid bilayer and factors that influence membrane fluidity

    • Explain how membrane composition affects permeability and cellular function

    • In-Class Activity: Design an experiment to test diffusion of proteins in a membrane (2pts)

Learning Objective #2
  • Protein structure–function relationships (focus on transmembrane proteins)

    • Describe the levels of protein structure and how they relate to function

    • Explain the topology and orientation of transmembrane proteins within membranes

    • In-Class Activity: Apply gained knowledge to understand and design biological research (2pts)

Membrane Structure and Composition

  • Typical Membrane Composition

    • Cellular membranes typically consist of a lipid bilayer dotted with proteins.

    • Components: Phospholipids, cholesterol, proteins

    • Examples of organelles defined by membranes include: (Figures of cell structure in slides are referenced)

    • Mitochondrion

    • Endosome

    • Lysosome

    • Golgi apparatus

    • Smooth Endoplasmic Reticulum

    • Rough Endoplasmic Reticulum

    • Nucleus

    • Plasma membrane

Phospholipids
  • Structure of Phospholipids:

    • Composed of a hydrophilic “head group” (including a phosphate group) and hydrophobic fatty acid “tails.”

    • Phospholipids are amphiphilic due to their dual nature.

    • Fatty Acids:

    • Can be saturated (no double bonds) or unsaturated (one or more double bonds).

    • Generally contain between 14-24 carbons.

  • Types of Phospholipids:

    • Phosphoglycerides:

    • Phosphatidylethanolamine (PE)

    • Phosphatidylserine (PS)

    • Phosphatidylcholine (PC)

    • Sphingolipids:

    • Sphingomyelin (SM)

    • Together, these phospholipids constitute about half of the lipid mass in cells.

Cholesterol
  • Role of Cholesterol in Membranes:

    • Major component of cellular membranes with a nearly 1:1 ratio with phospholipids.

    • Cholesterol influences

    • Membrane flexibility and permeability

    • Membrane thickness

Membrane Dynamics and Fluidity
  • Factors Affecting Membrane Fluidity:

    • Fatty acid chain length and saturation

    • Shorter and more unsaturated chains result in a thinner membrane, which is more fluid at lower temperatures.

    • Cold-adapted animals, such as icefish, maintain membrane fluidity with high unsaturation and flexibility in low temperatures.

Membrane Proteins

  • Types of Membrane Proteins:

    • Transmembrane (integral) proteins

    • Multi-pass transmembrane proteins

    • Peripheral proteins (attached via lipid side-chain or oligosaccharide linkage)

    • Membrane-associated proteins through interaction with other proteins

  • Functions of Membrane Proteins:

    • Junctions: Connect and join cells

    • Enzymes: Localize metabolic pathways by fixing to membranes

    • Transport: Facilitate diffusion and active transport

    • Recognition: Serve as cellular markers

    • Anchorage: Provide attachment points for cytoskeleton/extracellular matrix

    • Transduction: Function as receptors for hormones

Studying Membrane Dynamics

  • Fluorescence Recovery After Photobleaching (FRAP):

    • Technique to analyze the dynamics of proteins and lipids in membranes.

    • Method:

      • A specific area of a membrane is bleached using a laser, and recovery of fluorescence in the bleached area is monitored over time.

Cellular Compartments

  • Overview of Cellular Compartments:

    • Major Compartments and Their Functions:

    • Cytosol: 54% cell volume

    • Mitochondria: 22%

    • Rough Endoplasmic Reticulum: 9%

    • Smooth Endoplasmic Reticulum + Golgi: 6%

    • Nucleus: 6%

    • Peroxisomes: 1%

    • Lysosomes: 1%

    • Endosomes: 1%

  • Organelles with Membranes:

    • Single membrane organelles include lysosome, endoplasmic reticulum, and Golgi.

    • Double membrane organelles include chloroplast, nucleus, and mitochondria.

Topological Relationships in Organelles
  • Definition of a Cellular Compartment: The distinction between what is "inside" and "outside" a compartment.

  • Mechanism of Transport Between Compartments: Transport vesicles bud from one compartment and fuse with another.

Protein Structure

  • Levels of Protein Structure:

    • Primary Structure: Linear sequence of amino acids (the backbone of the polypeptide).

    • Secondary Structure: Regular substructures including alpha helices and beta sheets crucial for transmembrane proteins.

    • Alpha Helix: Formed by hydrogen bonds within the helix.

    • Beta Sheet: Formed by hydrogen bonds between adjacent strands.

    • Tertiary Structure: Three-dimensional shape, dependent on interactions between local and distant amino acids.

    • Quaternary Structure: Complex of multiple polypeptide chains.

Hydropathy and Membrane Proteins

  • Hydropathy Scale: Used to predict hydrophobic regions of proteins giving insights into transmembrane domains.

    • Positive values indicate hydrophobic regions, where stretches of 20+ amino acids may signify a transmembrane helix.

  • Hydropathy Plots:

    • Visual representations marking hydrophilicity/hydrophobicity across the polypeptide chain to identify potential membrane spanning segments.

Literature Suggestions

  • Review Chapters from MBOC:

    • Chapter on Membrane Structure

    • Chapter on Proteins

    • Chapter on Compartments

  • Focus on lecture slides for key learning points without delving too deeply into the text.

Types of Phospholipids:
  • Phosphoglycerides: These are the most common type of phospholipids and contain a glycerol backbone.

    • Phosphatidylethanolamine (PE): Important in cell membrane fluidity and involved in signaling.

    • Phosphatidylserine (PS): Plays a critical role in cell signaling and apoptosis; it is often found on the inner leaflet of membranes but flips to the outer leaflet during programmed cell death.

    • Phosphatidylcholine (PC): Major component of the lipid bilayer, it is involved in bilayer stability and membrane integrity; particularly abundant in the outer leaflet of cell membranes.

  • Sphingolipids: These are composed of a sphingosine backbone rather than glycerol, and they play key roles in membrane dynamics and signaling.

    • Sphingomyelin (SM): Found abundantly in the membranes of cells that make up the myelin sheath surrounding nerve cells, it is crucial for proper nerve function.

    • Glycosphingolipids: These contain carbohydrate moieties and are important for cell recognition and signaling processes.

    • Ceramides: Formed by the linkage of sphingosine and fatty acids, ceramides are involved in signaling pathways and cellular aging.

Together, these phospholipids constitute about half of the lipid mass in cells and contribute to the diverse functions of biological membranes.