Cellular Biology, Neurons, Bone, and Connective Tissues

Posted on Mar 19, 2025 in Human Biology

1. Cellular Structure & Function

  • Cell

    The smallest living unit, responsible for metabolism, reproduction, and response to stimuli. Composed of a plasma membrane, cytoplasm (organelles, cytoskeleton), and nucleus. “Continuity of life is based on cells” (Week 1, Lectures [103], [109]).

  • Plasma Membrane

    Structure: A phospholipid bilayer interspersed with proteins (integral, peripheral), cholesterol (for stability), and carbohydrates (glycocalyx for cell recognition).

    Functions:

    • Physical barrier and gateway for substances
    • Communication via membrane receptors
    • Provides anchoring for cell junctions

    Key Terms:

    • Glycocalyx: Outer carbohydrate layer that mediates cell–cell recognition and protects against mechanical stress.

2. Membrane Transport

  • Passive Transport

    • Simple Diffusion: Movement of small, lipid-soluble molecules (e.g., O₂) down a concentration gradient (no ATP required).
    • Facilitated Diffusion: Uses carrier proteins and ion channels (e.g., aquaporins for water) to move polar molecules; follows Fick’s Law.
    • Osmosis: Diffusion of water through a semi-permeable membrane driven by solute concentration differences.

  • Active Transport

    • Primary Active Transport: Direct use of ATP (e.g., Na⁺/K⁺ pump maintains resting membrane potential ~ –70 mV).
    • Secondary Active Transport: Utilizes ion gradients established by primary pumps (symporters & antiporters).

  • Key Factors

    Lipid solubility, molecular size, and concentration gradients affect diffusion rates (referenced in Week 2, Lect 3 [107]).

3. Signal Transduction

  • Process

    • Ligand Binding: A chemical messenger (ligand) binds to a specific receptor (e.g., GPCR, enzyme-linked, receptor channel, integrin).
    • Cascade: Binding activates intracellular signals that lead to protein modification or gene transcription.

  • Modulation

    • Up/Down-Regulation: Adjusting receptor numbers or binding affinity (explained in Week 3, Lect 4 [106]).
    • Agonists/Antagonists: Agonists mimic the natural ligand; antagonists block receptor activation.

  • Quiz Focus

    Be able to define these processes and describe an example (e.g., receptor activation leading to a cellular response).

1. Neuron Structure & Function

  • Neuron Components

    • Dendrites: Receive incoming signals.
    • Soma (Cell Body): Contains nucleus, Nissl bodies (sites of protein synthesis).
    • Axon: Conducts electrical impulses; includes the axon hillock (initiation zone) & Nodes of Ranvier (saltatory conduction).
    • Axon Terminals: Release neurotransmitters into the synaptic cleft.

  • Action Potential

    • Depolarization: Opening of voltage-gated Na⁺ channels leads to Na⁺ influx (down both concentration & electrical gradients).
    • Repolarization: Inactivation of Na⁺ channels & opening of K⁺ channels causes K⁺ efflux.
    • All-or-None Law: Once threshold is reached, an action potential is generated with constant amplitude regardless of stimulus strength.

  • Quiz Example

    (Quiz Q5, Q6 from Week 6; see also [89]).

2. Glial Cells

  • Types & Functions

    • CNS:
      • Astrocytes: Support neurons, maintain the blood-brain barrier (BBB), regulate ion balance & neurotransmitter uptake.
      • Oligodendrocytes: Form myelin sheaths in the CNS.
      • Microglia: Act as immune cells, clearing debris & pathogens (e.g., in meningitis [Quiz Q1]).
      • Ependymal cells: Line the ventricles; act as neural stem cells.
    • PNS:
      • Schwann Cells: Myelinate peripheral axons; facilitate rapid impulse conduction.
      • Satellite Cells: Support peripheral neuron cell bodies.

3. Axonal Transport

  • Definitions

    • Fast Axonal Transport: Transports membranous organelles @ 200–400 mm/day; bidirectional (anterograde & retrograde).
    • Slow Axonal Transport: Transports proteins & cytoskeletal elements @ 0.2–2.5 mm/day (typically anterograde only).

  • Clinical Relevance

    Some pathogens (rabies, tetanus) exploit retrograde transport (Week 6, Lect 1, [89]).

4. Resting Membrane Potential & Ion Channels

  • Resting Membrane Potential (RMP)

    ~–70 mV, maintained by the Na⁺/K⁺ pump & leak channels.

  • Key Equations

    • Nernst Equation: Calculates the equilibrium potential for a specific ion.
    • Goldman-Hodgkin-Katz Equation: Considers multiple ions to predict RMP.

  • Quiz Focus

    Understand the mechanisms behind RMP & how an action potential is generated (Quiz Q5, Q6).

1. Bone Functions & Composition

  • Functions of Bone

    Structural support, protection, movement (lever system), hematopoiesis (red marrow), storage of minerals (calcium, phosphorus), triglyceride storage, & hormone production (osteocalcin for metabolism regulation) ([106]).

  • Bone Composition

    • Mineral Phase (~70%): Mainly hydroxyapatite (provides hardness & resistance to compression).
    • Organic Matrix (~18%): Mainly Type I collagen (provides tensile strength & flexibility).
    • Water (~10%): Contributes to bone’s viscoelasticity.

2. Bone Structure & Microarchitecture

  • Macroscopic Structure

    • Cortical (Compact) Bone: Dense, forms the outer shell, low porosity (5–30%).
    • Trabecular (Spongy) Bone: Porous, forms inside, higher porosity (50–95%), arranged along lines of stress (Wolff’s law).

  • Microscopic Structure

    • Haversian Systems (Osteons): Concentric lamellae surrounding central canals (Haversian canals) that house blood vessels, nerves, & lymphatics; interconnected by canaliculi linking osteocytes ([106]).

  • Bone Cells

    • Osteoblasts: Build bone matrix.
    • Osteoclasts: Resorb bone matrix.
    • Osteocytes: Mature bone cells residing in lacunae, interconnected by canaliculi ([106]).

  • Quiz Focus

    Be familiar with quiz matching questions (e.g., matching osteoblasts, osteoclasts, endosteum, lamellae, & canaliculi).

3. Bone Growth & Remodeling

  • Longitudinal Growth

    • Occurs at the epiphyseal (growth) plate via endochondral ossification.
    • Growth stops when the epiphyseal plate fuses (females ~18, males ~21).

  • Appositional Growth

    • Bone thickening through osteoblast activity under the periosteum.
    • Governed by Wolff’s Law: Bone adapts to mechanical stress by changing its architecture.

  • Bone Remodeling

    • Continuous cycle balancing deposition (osteoblasts) & resorption (osteoclasts).
    • Trabecular bone remodels faster than cortical bone.

  • Fracture Healing Stages

    1. Hematoma formation
    2. Fibrocartilaginous callus formation
    3. Bony callus formation
    4. Remodeling (restores original structure) ([122], [123]).

1. Soft Connective Tissues

Tendons, Ligaments, & Cartilage

  • Tendons

    Connect muscle to bone; transmit force for movement.

    Composed mostly of Type I collagen (75–85% dry weight); fibers are highly aligned, providing stiffness & strength.

    Key Structure: Hierarchical organization (tropocollagen → microfibrils → fibrils → fiber bundles → fascicles) & enveloped by endotenon/epitenon ([121]).

  • Ligaments

    Connect bone to bone; provide joint stability with slightly higher elastin for flexibility.

    Denser than tendons with a twisted fiber arrangement.

  • Cartilage

    Types include articular (hyaline) cartilage, fibrocartilage, & elastic cartilage.

    • Articular Cartilage: Covers bone ends; zonal organization:
      • Superficial Zone: Collagen fibers parallel to surface for smooth gliding.
      • Transitional Zone: Randomly dispersed collagen; high proteoglycan & water content for compressive strength.
      • Deep Zone: Collagen fibers perpendicular to the surface, anchoring cartilage to bone ([104]).

    Avascular tissue with low regenerative capacity; often tissue engineered.

  • Joints

    Classified functionally as synarthrosis (immovable), amphiarthrosis (slightly movable), & diarthrosis (freely movable, e.g., synovial joints).

    • Synovial Joints: Characterized by a synovial cavity, articular cartilage, & joint capsule (fibrous & synovial layers), lubricated by synovial fluid.

2. Applied Problems & Discussion Points

  • Corneal Staining & Wound Dressings

    • Hydrogel Dressings: Limitations include lack of biological components (cells, growth factors), insufficient barrier properties, weak mechanical integrity, frequent changes, & poor infection prevention ([126]).
    • Design Requirements for Tissue-Engineered Skin: Must be biocompatible, mechanically mimic skin (elasticity, strength), support cell adhesion & proliferation, be permeable for oxygen diffusion, anti-bacterial, hypoallergenic, cost-effective, & FDA-approved.

  • Bone Applied Problems

    • Osteoporosis: Even with normal blood Ca²⁺ levels, bone density can be low due to increased osteoclast activity. (Quiz Q? from [122]).
    • Exercise for Bone Health: Weight-bearing activities (e.g., walking, light lifting) are more effective than swimming because mechanical stress stimulates bone remodeling (Wolff’s law).
    • Fracture & Running: A small defect in cortical bone may lead to crack propagation under cyclic loading (stress fractures).
    • Implant Design Challenges: Mismatch of mechanical properties between implant & bone (e.g., Titanium Alloy vs. bone Young’s modulus) can lead to stress shielding, poor osseointegration, or abnormal bone growth ([122], [123]).

  • Tendon & Ligament Healing

    • Slow healing due to limited vascularity; immobilization can improve tissue organization compared to active motion (discussed in class activities [121]).
    • Stress–strain curves indicate that tendon tissue regains stiffness over time with proper healing.

3. Key Equations & Concepts

  • Fick’s Law of Diffusion: Rate ∝ (Concentration Gradient)/(Distance)
  • Nernst Equation: E = (RT/zF) ln([ion]_out/[ion]_in)
  • Goldman-Hodgkin-Katz Equation: Incorporates permeabilities & concentrations of multiple ions to calculate membrane potential.