Biological Membranes and Phospholipids Quiz

Prokaryotic vs. Eukaryotic Cells

• Prokaryotic cells lack internal organelles, while eukaryotic cells do have them.
• Cell walls are present in prokaryotic cells, but not in eukaryotic cells.
• Flagella are present in prokaryotic cells, absent in eukaryotic cells.

Organelle Functions

• Organelles are specialized structures in cells with specific functions.
• Cell membranes separate intracellular and extracellular environments.
• Membranes act as selective permeability barriers.
• Membranes regulate biochemical processes in different cell compartments.

Membrane Compartmentalization

• Increases the efficiency of biochemical reactions in the cell by increasing local substrate concentration.
• Segregates anabolic and catabolic reactions into different compartments
• Examples include fatty acid synthesis (in cytosol) and fatty acid oxidation (in mitochondria).

Conventional Cellular Compartments

• Nucleus: Houses genetic information.
• Ribosomes: Protein synthesis.
• Rough Endoplasmic Reticulum (RER): Protein synthesis and processing.
• Smooth Endoplasmic Reticulum (SER): Lipid synthesis.
• Golgi Apparatus: Protein processing.
• Lysosomes: Digestion and recycling.
• Peroxisomes: Oxidation of fatty acids.
• Vacuoles: Storage of oils, carbs, waters, or toxins.
• Mitochondria: ATP production.
• Chloroplasts: ATP and sugar production via photosynthesis.
• Cytoskeleton: Structural support and cell movement.
• Plasma Membrane: Selective permeability, maintains a suitable intracellular environment, and provides structural support.
• Cell Wall: Protection and structural support (in plant cells).

RNA Granules

• Nucleoprotein granules that contain RNA and proteins
• Important for cellular function in nucleus and cytoplasm
• Disintegrate when RNase-L activates.

Lipid Droplets

• Considered organelles now.
• Molecular aggregates found in cells.

Composition of Membranes

• Membranes are composed of lipids, proteins, and carbohydrates.
• Glycerophospholipids make up 3 classes of lipids.
• Sterols, sphingolipids, and glycerophospholipids are lipids.
• Proteins (including glycoproteins and glycolipids), are also components.
• The lipid to protein ratio affects the biological activity of membranes.

Glycerophospholipids (GPLs)

• Glycerol is the backbone of GPLs.
• The head group is attached to the phosphate group of glycerol by an ester-linkage.
• Fatty acid tails are attached to positions C-1 and C-2.

Polyunsaturated Fatty Acids (PUFAs)

• Examples are EPA, DHA, and arachidonic acid.
• More than one double bond (db)
• Numbering starts at the carboxyl end (COOH)
• "Omega-#" numbering starts at the methylated end (CH3)

Unsaturation Effects

• More unsaturated FAs= decrease in melting temperature.
• This is due to the "bent chain" structure of unsaturated fatty acids.
• This can lead to the decreased membrane viscosity in membranes.

Sphingolipids

• "Backbone" sphingosine is an amino alcohol.

Membrane Lipids

• Amphipathic (polar head, and nonpolar tail)
• Hydrophobic effect= spontaneous assembly into structured in mixed lipid-water systems
• Maximizes NP-NP and P-P interactions
• Minimizes overall energy from water/low entropy
• Organize into: bilayers, liposomes/vesicles, and micelles

Historical Perspectives

• Overton= relation of membrane passage to chemical nature.
• Danielli-Davson model= a sandwich-like model of membrane structure (globuler proteins above and below hydrophobic bilayer)
• Robertson's unit membrane hypothesis= true about all cell membranes
• Singer-Nicolson's fluid mosaic model: proteins "float" within plane of membrane, and can move freely within cell's bilayer
• Detergents disrupt protein-lipid interactions and denature them (preventing protein and lipid interaction for separation via centrifugation)

General Composition

• The composition of membranes vary in different cell types and subcellular compartments
• Generally, proteins to lipid ratio is higher in higher biological activity.

Cell Compartmentalization and Functions

• Cells are compartmentalized to optimize biochemical processes and protect cellular structures.

Protein Transport and Localization

• Cytosolic proteins are destined to be translocated to mitochondria, are primarily unfolded.
• These proteins are coated by chaperone proteins that maintain their unfolded state until reaching the mitochondria's interior and use specific signal sequences to target their desired destination.
• The process usually requires some form of energy transfer.
• The outer and inner membranes of the mitochondria have protein translocators (TOM and TIM).

Protein Signal Sequences

• N-terminal signals initiate import into matrix
• Hydrophobic signal= stops translocation when it binds to the TIM23 complex
• Second signal= directly into the inner membrane using OXA complex.
• Signal sequences give protein polarity.

Protein Sorting in the ER

• Protein translation begins in cytosol, then mRNA is exported to the cytoplasm to be recognised by exportin proteins which then exits the nucleus.
• The signal recognition protein (SRP) binding to a signal sequence on a growing polypeptide halts the translation.
• This also targets the growing polypeptide chain into the ER lumen= co-translational translocation of protein into the ER.
• ER signal sequences help transport protein complexes by recognising ribosomes or membrane into the ER
• After synthesis, the polypeptide enters the ER lumen, and signal peptidase cuts of the signal sequence.

Vesicular Trafficking

• Endocytosis: uptake of extracellular material into vesicles (e.g., clathrin-mediated endocytosis).
• Exocytosis: release of material from vesicles to the extracellular environment (e.g., secretory vesicles).
• Proteins and lipids are sorted in the ERs and Golgi complex based on addresses for sorting in different compartments.
• Vesicles carry cargo as they are transported according to targeting signals
• COP is used for sorting of vesicles directed from ER to Golgi and vice versa
• The signal sequence is processed before the polypeptide enters the ER lumen

Protein Glycosylation

• Glycosylation is critical in the ER and Golgi, involving the addition of sugars to proteins to modify their structure, function, and targeting
• Various glycosylation types (N-linked, O-linked) occur with different pathways to form glycoprotein
• Functions of glycosylation include quality control or protein folding, interaction, and delivery of proteins, and in some cases, altering the proteins’ solubility

Retrieval

• ER-resident proteins (e.g., proteins with KDEL sequence) are retrieved from the Golgi complex to the ER by transport vesicles.

Hydrophobic effect

• Lipids in aqueous solutions are driven by minimizing the free energy via formation into organized structures
• Minimizes free energy and maximizes favorable interactions (polar-polar and nonpolar-nonpolar)

Biophysical Methods

• Microscopy
• Spectroscopy
• X-ray diffraction
• Biochemical methods (e.g., immunofluorescence and chemical modification)

Polarity

• Establishing cell polarity in development involves asymmetric distribution of proteins and lipids. • Mechanisms of polarity include breaking symmetry, recruitment of specific proteins and polarisation of the cytoskeleton, and vesicles.

Cell Polarity and Maintenance

• Cells maintain their polarity state through the interaction of proteins and lipids, and through the maintenance and reinforcement of polarized states through the establishment of polarity in various cellular functions

Cell Junctions

• Various types of cell junctions like adherens junctions and desmosomes.
• Cadherins= transmembrane proteins that facilitate cell-cell adhesion
• Integrins= transmembrane proteins that facilitate cell-ECM adhesion
• Junctions play critical roles in establishing and maintaining cell polarity

Polarized Cytoskeleton

• Microtubules (MTs) are uniformly polarized and are responsible for directional transport in cells.
• Reinforce polarity by establishing directionality and movement
• Golgi, ER, and Nucleus position are consistent and directional depending on position in a cell.

Core PCP complex

• Establishes and maintains planar cell polarity.

Signal Transduction and Cellular Communication

• Signal transduction= instrumental in cellular adaptation and survival.
• Exosomes= mechanisms for transfer of intracellular components.
• Proteins= dynamic structural fluctuations.
• Cellular and intercellular communication are driven by basic survival needs.
• Cellular communication relies on signaling molecules.

Signal Transduction Contexts

• Signal transduction is used by cells to adapt and survive.
• Cells use several types and timing of signal transduction.
• Cells use compartments to control signal and pathway.
• Cells employ feedback loops and cross-talk between signaling pathways.
• Biomolecular condensates serve as highly dynamic and specific signaling centres.

Types of Post-Translational Modifications (PTMs)

• Acetylation, Methylation, Phosphorylation, Ubiquitination, Sumoylation, and S-nitrosylation can alter protein activity, localization, binding interactions, and even stability, all regulating its downstream function.

Cell Cycle Checkpoints

• Ensure cell cycle progression is correct.
• Stops cell cycle if there are any issues
• Specific proteins are crucial to detect and respond to DNA errors and damages

Cell Cycle Regulation

• Cyclin-dependent kinases (CDKs)= regulate cell cycle progression by phosphorylation of target proteins
• Cell cycle checkpoints= ensure that errors don't progress to downstream stages= critical for preventing cell cycle progression in the presence of DNA damage

Pathways of DNA Damage Sensing and Repair

• The recognition of DNA damage triggers a complex cascade of events to repair DNA.
• This involves the activation of kinases such as ATM and ATR to phosphorylate proteins that eventually lead to cell cycle arrest/repair.

Apoptosis

• Initiated by caspases- cysteine proteases that cleave specific cell substrates.
• These enzymes result in cellular components being degraded and the cell is signalled to be eliminated (apoptosome)
• Apoptosis is a critical mechanism for eliminating cells with damaged DNA, preventing their propagation.

Stem Cell Types and Differentiation

• Totipotent (zygotes), Pluripotent (ES cells), Multipotent (hematopoietic), Oligopotent (neural), and unipotent stem cells (muscle, erythrocytes)= specific potency in differentiation
• Differentiated by DNA methylation (open or closed chromatin); chemicals, mechanical forces, and cytokines
• Cytokine, chemical or mechanical forces are used to promote or prevent differentiation.

Introduction to iPSCs

• Induced pluripotent stem cells= normal somatic cells transformed to a stem cell (pluripotent) with 4 transcription factors.
• Common delivery methods are adenovirus, lentivirus and sendaiviruses.

Basic Principles of Animal Research

• Ethical rules must be followed in animal research.
• Research should only be conducted if it follows ethical guidelines and is scientifically relevant.

Test your knowledge on the structure and function of biological membranes, particularly focusing on phospholipids. Explore topics such as the Danielli-Davison Model, cytoskeleton functions, and the role of lipids and proteins in membrane dynamics. This quiz is essential for understanding cellular biology and membrane biochemistry.