Cell Biology: Organelles, Cell Cycle, and Differentiation (Lecture Notes)

Cytosol vs Cytoplasm

• Cytosol: gel-like fluid inside the cell.
• Cytoplasm: cytosol plus all other cellular contents except the nucleus.
• Common confusion: cytosol ≈ fluid; cytoplasm ≈ fluid + organelles (excluding nucleus).
• Cytoplasmic inclusions: various substances suspended in the cytosol.

Cytoskeletal Elements: Structure and Movement

• Cytoskeleton provides structure and shape to the cell (like pillars in a room).
• Major components by size:
  • Microtubules (largest): used for shape, transport, and mitotic spindle formation.
  • Intermediate filaments: provide tensile strength (e.g., keratins, vimentin).
  • Microfilaments (actin): support cell shape and enable movement and cytokinesis.
• Other structural elements:
  • Centrioles: organize the mitotic spindle during cell division.
  • Cilia (stilia): hair-like extensions that move fluid or particles across cell surfaces.
  • Flagella: tail-like structure used for cell movement in some cells.
• When fluorescently labeled, microtubules (green), actin (red), and keratins (another color) can be visualized.

Nucleus, DNA, and Nuclear Transport

• The nucleus houses DNA and is surrounded by the nuclear envelope (a double phospholipid bilayer).
• Nuclear pores allow selective traffic in and out (RNA export, some protein import).
• Nucleolus: subregion inside the nucleus where ribosomal RNA (rRNA) is synthesized.
• DNA structure: double-stranded helix; in most of a cell’s life it’s relaxed as chromatin; before division it condenses into chromosomes.
• Red blood cells (RBCs): mature RBCs lack a nucleus, maximizing space for hemoglobin; they do not repair DNA or divide.
• Spleen: recycles old RBCs; old RBCs get trapped in narrow vessels and are broken down.
• DNA replication enzymes (brief mention):
  • DNA helicase unwinds the double helix.
  • DNA polymerase synthesizes new DNA strands.
• DNA content before division: human somatic cells are diploid with 23 pairs of chromosomes, i.e. 2n=46\,\text{chromosomes}; hence n=23 (haploid).
• In preparation for division, DNA is replicated, producing sister chromatids; after replication, a cell has 46 chromosomes but 92 chromatids (two sister chromatids per chromosome): \text{chromosomes} = 46, \ \text{chromatids} = 92 = 2\times 46.

RNA, Transcription, Translation, and the Genetic Code

• Gene = recipe for a protein; DNA serves as the cookbook.
• Transcription: DNA is copied into messenger RNA (mRNA); occurs in the nucleus, with the nucleolus involved in RNA synthesis.
• Translation: mRNA is read by ribosomes to assemble amino acids into a protein; happens at ribosomes, with transfer RNA (tRNA) bringing amino acids.
• Codons: sequence of three bases in mRNA that code for a specific amino acid; a codon = 3 bases, e.g. three-base units determine the amino acid added next.
• Anticodon: the complementary three-base sequence on tRNA that pairs with the mRNA codon during translation.
• Primary protein structure: the single string of amino acids produced by the ribosome.
• Protein folding: after synthesis, proteins fold into secondary (folds and helices), tertiary (3D shape), and quaternary structures (assembly of multiple chains).
• Sequence example concept: A codon is a three-base unit; different codons specify different amino acids in protein synthesis.
• Substitution example (sickle cell): a single base change can substitute one amino acid (e.g., valine) for another (e.g., serine), altering protein structure and function; this can be an evolutionary adaptation in some contexts but may cause disease (malaria resistance vs. anemia risk).
• On the topic of codons: anticodon is complementary to the mRNA codon; transfer RNA recognizes codons via anticodons.
• Note: The instructor may mention that codons map to amino acids; in practice, the genetic code contains 64 codons mapping to 20 amino acids and stop signals.

Endomembrane System and Protein Processing

• Rough Endoplasmic Reticulum (RER): studded with ribosomes; site of protein synthesis and initial processing/proper folding of proteins.
• Smooth Endoplasmic Reticulum (SER): lacks ribosomes; involved in lipid synthesis and carbohydrate metabolism, among other roles.
• Golgi apparatus: packages and tags proteins and lipids for delivery; forms transport vesicles to send products to their destinations (within cell or to the cell membrane for secretion).
• Vesicle trafficking and exocytosis: vesicles can fuse with the plasma membrane to release contents outside the cell; requires ATP for active transport.
• “Form follows function”: organelle roles are tied to their structure and location within the cell.

Lysosomes, Autophagy, and Cellular Quality Control

• Lysosomes contain lytic enzymes that break down biomolecules and worn-out cell parts.
• Degradation processes:
  • Dehydration synthesis (a.k.a. dehydration synthesis) builds molecules with loss of water.
  • Hydrolysis uses water to break bonds.
• Autophagy: cells digest and recycle their own damaged organelles via lysosomal enzymes.
• Cellular senescence: cells eventually lose the ability to divide and may enter a non-dividing state.
• Apoptosis: programmed cell death triggered when cellular components fail to function properly or when cells are damaged beyond repair; excessive or insufficient apoptosis can contribute to cancer.
• Tumors: enlarged masses of cells; can be benign (non-cancerous) or malignant (cancerous).

Mitochondria and Energy Production

• Mitochondria are the powerhouses, producing the majority of cellular ATP.
• Metabolic processes include the Krebs cycle (citric acid cycle) and the electron transport chain (ETC) with oxidative phosphorylation.
• Oxygen usage drives the ETC; outputs include carbon dioxide and water, plus ATP.
• The instructor notes that metabolism and respiration (metabolism/respiration) occur in mitochondria; FRET cycle mentioned but typically refers to fluorescence resonance energy transfer used in some imaging studies (not a metabolic cycle).
• Peroxisomes: detoxify reactive oxygen species (ROS) and other peroxides; help mitigate free radicals; important for cellular redox balance.
• Free radicals and ROS: reactive oxygen species that can damage cells if not regulated; peroxisomes help maintain homeostasis.
• Lab accessibility tip: color vision can impact the interpretation of color-coded organelle models; if color-blind, inform the lab instructor for accommodation.
• Peroxisomes vs. Lysosomes metaphors: candy analogies used to help visualize these organelles (paroxysome vs. lysosome) in class; internal labeling may differ in real images.

The Nucleus in More Detail

• Nuclear envelope: two phospholipid bilayers (double membrane) that enclose the nucleus; sometimes described as a “double double” layer.
• Nuclear pores: gateways for selective transport of RNA, proteins, etc.
• Nucleolus: site of ribosomal RNA (rRNA) synthesis and ribosome assembly components.
• Chromatin vs chromosomes:
  • Interphase: DNA is uncoiled as chromatin (loosely packed) for transcription.
  • Mitosis: DNA condenses into chromosomes for segregation.
• Erythrocytes (RBCs) lack a nucleus, which precludes DNA replication and repair; this is a specialization to maximize oxygen transport.
• Diabetic considerations: hemoglobin A1c (HbA1c) is a lab test reflecting average blood glucose over ~3 months and can indicate damage to RBCs and vascular complications.
• Chromosome organization and dynamics: during mitosis, chromosomes condense; spindles attach to kinetochores to segregate chromatids.
• DNA and replication enzymes (brief):
  • Helicase unzips DNA.
  • DNA polymerase copies DNA.
• The three processes to move genetic information: transcription (DNA to mRNA), RNA processing, translation (mRNA to protein).

The Cell Cycle, Mitosis, and Cytokinesis

• Cellular life cycles: Interphase (growth and activity) followed by mitosis and cytokinesis.
• Interphase components:
  • G1 phase: cell grows.
  • S phase: DNA replication; synthesis of DNA content doubles.
  • G2 phase: cell grows again and prepares for division.
  • G0: cells that have exited the cell cycle (non-dividing) (e.g., many neurons).
• Not all cells divide: some cells remain in G0 (e.g., many neurons).
• Mitosis phases (memory aid): “Please Make A Telephone Call” for Prophase, Metaphase, Anaphase, Telophase; Cytokinesis is the physical split of the cytoplasm.
  • Prophase: chromosomes condense; nuclear envelope breaks down; mitotic spindle forms.
  • Metaphase: chromosomes align at the cell equator, attached to spindle microtubules.
  • Anaphase: sister chromatids separate and are pulled toward opposite poles.
  • Telophase: chromosomes de-condense; nuclear envelope re-forms; spindle disassembles.
  • Cytokinesis: cytoplasm divides, resulting in two identical diploid daughter cells.
• Outcome: two genetically identical daughter cells in mitosis; after cytokinesis, cells re-enter interphase.
• G2 checkpoint and regulation: cells ensure DNA is replicated correctly before mitosis proceeds.
• Special cases:
  • Muscle and nerve cells: often do not divide after differentiation (post-mitotic).
  • Hematopoietic stem cells: can be multipotent and differentiate into various blood cell lineages.

Growth, Differentiation, and Potency

• Differentiation: cells commit to a specific lineage and function.
• Potency spectrum:
  • Totipotent: can become any cell type (including placenta and embryo proper).
  • Pluripotent: can form many cell types but not extra-embryonic tissues.
  • Multipotent: can form multiple cell types within a lineage (e.g., hematopoietic stem cells can become red blood cells, white blood cells, platelets).
  • Oligopotent: can become a few different cell types (restricted lineage).
  • Unipotent: can differentiate into only one cell type (e.g., mature liver cells produce more liver cells).
• Hematopoietic stem cell example: can become myeloid or lymphoid lineages; left/right branching defines potential paths (e.g., myeloid vs lymphoid progenitors).
• Cancer and oncogenesis: mutations in genes controlling cell division can lead to cancer; an oncologist treats cancer.
• Tumors and neoplasms: benign vs malignant; fibromas, lipomas are benign; malignant tumors invade and metastasize.

Practical and Real-World Connections

• Form follows function: organelle structure dictates its function in the cell.
• Energy and pathology: mitochondrial function is central to ATP production and overall metabolism; ROS balance is critical for cellular health.
• Lab and study tips:
  • If you’re color-blind, inform your lab instructor for accessible visuals.
  • Use mnemonics to remember mitosis order (P-M-A-T-C for stages and Cytokinesis separately).
  • Relate concepts to real-world examples (e.g., RBCs’ lack of nucleus relates to oxygen transport; spleen’s role in recycling aged RBCs).
• Ethical/philosophical implications: understanding cellular differentiation and cancer informs medical ethics, treatment choices, and the societal impact of oncology research.

Quick Reference: Key Numbers and Facts (LaTeX format)

• Humans have 23 pairs of chromosomes: 2n=46,\quad n=23
• After DNA replication during S phase: the cell contains 46 chromosomes but 92 chromatids: ext{chromosomes}=46,\ \text{chromatids}=92=2\times 46
• Codon length in mRNA: ext{codon} = 3\ \text{bases}
• Interphase subphases: G1, \ S, \ G2, \ G_0
• RBC lifespan: 90-120\ \text{days}
• Oxygen consumption and CO2 production occur in mitochondria during cellular respiration: \text{O}2 + \text{glucose} \rightarrow \text{CO}2 + \text{H}_2\text{O} + \text{ATP}
• Mitochondria produce the majority of cellular ATP via oxidative phosphorylation and the ETC.
• RBCs lack nuclei (and mitochondria) to maximize oxygen transport; RBCs do not divide.

Accessibility and Study Strategy Notes

• If a model image uses color coding, verify if you can distinguish colors; request alternative labeling if needed.
• Use the provided mnemonics to memorize lists (e.g., mitosis stages).
• Build connections across chapters: organelle functions, the cell cycle, energy metabolism, and disease mechanisms (oncogenesis, tumors, and stem cell differentiation).
• When studying, create flashcards for key terms: cytosol, cytoplasm, cytoskeleton components, nucleus, nucleolus, chromatin vs chromosomes, transcription, translation, codon, anticodon, ribosome, RER, SER, Golgi, lysosome, autophagy, lysosome vs peroxisome, mitochondria, ROS, RBCs, spleen, interphase phases, mitosis stages, cytokinesis, differentiation, potency levels, oncogenesis, neoplasm, and HbA1c.