Cell Membranes, Transport, Endomembrane System, and Cytoskeleton: Structured Study Notes

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Cell Membranes

Major Biological Functions

The cell membrane is a dynamic structure essential for maintaining cellular integrity and function. Its primary roles include:

Selective permeability: Controls the entry and exit of substances.
Compartmentalization: Separates cellular processes into distinct regions.
Transport: Facilitates movement of molecules across the membrane.
Signal transduction: Transmits signals from the environment to the cell interior.
Cell recognition: Enables cells to identify and interact with each other.
Structural anchoring: Provides attachment points for cytoskeletal elements.

Fluid Mosaic Model

The fluid mosaic model describes the structure of the cell membrane as a flexible bilayer of lipids with embedded proteins. Key points include:

Lipid bilayer: Formed due to the amphipathic nature of lipids.
Proteins: Embedded within the bilayer, contributing to the mosaic aspect.
Lateral movement: Demonstrated by FRAP (Fluorescence Recovery After Photobleaching).
Membrane asymmetry: Different composition between inner and outer leaflets.

Lipids provide fluidity, while proteins create the mosaic pattern.

Membrane Components

Phospholipids
Glycolipids
Sterols: Cholesterol (animal), ergosterol (fungal)
Integral proteins: Span the membrane
Peripheral proteins: Attached to membrane surface
Glycoproteins: Proteins with carbohydrate chains

Phospholipids

Phospholipids are the main structural component of membranes:

Structure: Glycerol backbone, two fatty acid tails (hydrophobic), phosphate head (hydrophilic)
Amphipathic: Contains both hydrophobic and hydrophilic regions
Bilayer formation: Hydrophobic tails face inward, hydrophilic heads face outward

Cholesterol

Cholesterol is an amphipathic sterol that modulates membrane fluidity:

Inserts between phospholipids
Buffers fluidity: prevents rigidity at low temperatures and excess fluidity at high temperatures

Membrane Fluidity Factors

Temperature: Higher temperature increases fluidity
Fatty acid length: Shorter chains increase fluidity
Saturation: Unsaturated (double bonds) increase fluidity
Cholesterol: Buffers fluidity

Lipid Rafts

Lipid rafts are microdomains enriched in cholesterol and sphingolipids:

More ordered and less fluid
Serve as platforms for cell signaling

Glycoproteins & Glycolipids

Carbohydrate chains attached to proteins and lipids face the exoplasmic side:

Involved in cell recognition
Determine ABO blood type

Blood Type	Sugar Addition	Transfusion Compatibility
O	No additional sugars	Universal donor
AB	Both sugars	Universal recipient

Membrane Asymmetry

Lipid distribution differs between leaflets
Proteins maintain orientation
Flip-flop movement is rare and requires flippases

Detergents

Detergents solubilize membrane proteins by surrounding hydrophobic regions.

SDS-PAGE

Separates proteins by size
SDS denatures proteins and imparts a uniform negative charge

FRAP (Fluorescence Recovery After Photobleaching)

Measures lateral mobility of membrane components
Photobleaching followed by recovery rate indicates fluidity

Transport Across Membranes

Diffusion

Diffusion is the passive movement of molecules down their concentration gradient.

Simple diffusion: No protein required
Facilitated diffusion: Requires membrane protein
Both are passive processes

Passive vs Active Transport

Passive: Down gradient, no ATP required
Active: Against gradient, requires energy

Primary Active Transport

Direct ATP usage
Example: Na+/K+ pump

Secondary Active Transport

Uses ion gradient established by primary active transport
Can be symport (same direction) or antiport (opposite direction)

Symport vs Antiport

Type	Direction	Example
Symport	Same direction	Na+/glucose transporter
Antiport	Opposite direction	Cl-/HCO3- exchanger

Carrier vs Channel Proteins

Carrier: Undergoes conformational change, saturable, can be uniport, symport, or antiport
Channel: Forms a pore, faster, often gated

Osmosis

Osmosis is the movement of water across a membrane, often facilitated by aquaporins.

Tonicity

Condition	Effect on Cell
Hypertonic	Cell shrinks
Hypotonic	Cell swells
Isotonic	No net change

RBC Transport Examples

O2 via simple diffusion
Cl-/HCO3- antiporter
Water via aquaporins

Endomembrane System and Protein Sorting

Components of the Endomembrane System

The endomembrane system is a network of membranes within eukaryotic cells, responsible for protein and lipid synthesis, modification, and transport.

Nuclear envelope
Rough ER
Smooth ER
Golgi apparatus
Lysosomes
Vesicles
Note: Chloroplasts are not part of the endomembrane system.

Rough ER

Synthesizes membrane, secreted, and lysosomal proteins

Smooth ER

Lipid synthesis
Detoxification
Ca2+ storage

Cotranslational Translocation

Protein translation and ER insertion occur simultaneously
Occurs at rough ER

Protein Synthesis Locations

Location	Protein Types
ER	Secreted, membrane, lysosomal, ER resident
Cytosol	Cytosolic, nuclear, mitochondrial, peroxisomal

Protein Topology

Signal-anchor (SA) and stop-transfer (STA) sequences are hydrophobic
Orientation is preserved during trafficking
N-terminus facing cytosol in ER remains cytosolic at plasma membrane

Golgi Apparatus

Cis: receiving side
Medial: modifying side
Trans: shipping side

Vesicle Budding Components

GTP-binding protein
Coat protein (selects cargo)
v-SNARE
Cargo protein
Cargo receptor
Note: t-SNARE is not part of budding

Vesicle Targeting

Rab GTPases identify target
v-SNARE binds t-SNARE
Membrane fusion follows

Anterograde vs Retrograde Transport

Type	Direction	Purpose
Anterograde	ER → Golgi → Plasma membrane	Forward transport
Retrograde	Golgi → ER	Returns escaped ER proteins

KDEL Sequence

ER retention signal
If protein reaches Golgi, KDEL sequence ensures return to ER

Receptor-Mediated Endocytosis

Specific ligand binding
Clathrin coat formation
Endosome formation

Lysosome

Acidic environment
Contains hydrolytic enzymes
Responsible for recycling and degradation

Cytoskeletal Systems

Cytoskeleton Definition

The cytoskeleton is a network of protein filaments that provides structural support, facilitates transport, enables cell division, and drives cellular movement.

Structure
Transport
Division
Movement

Microfilaments (Actin)

Smallest cytoskeletal element
Double helix structure
Polar (plus and minus ends)
Treadmilling: simultaneous growth at one end and shrinkage at the other
Functions: muscle contraction, contractile ring in cytokinesis

Myosin

Motor protein for actin
Myosin II is bipolar and involved in muscle contraction
Moves toward the plus end of actin filaments

Muscle Contraction Mechanism

Ca2+ binds to troponin
Tropomyosin shifts position
Myosin binds to actin
Power stroke occurs
Actin filaments slide past myosin

Microtubules

Largest cytoskeletal element
Composed of α and β tubulin dimers
Protofilament: linear chain of tubulin dimers
13 protofilaments form a hollow tube
Polar structure
Exhibit dynamic instability
Originate from MTOC (Microtubule Organizing Center)
Form mitotic spindle during cell division

γ-TuRC (Gamma Tubulin Ring Complex)

Nucleates microtubules
Anchors minus end

Mitotic Spindle Types

Kinetochore microtubules: attach to chromosomes
Polar microtubules: interact with other spindle microtubules
Astral microtubules: anchor spindle to cell cortex

Motor Proteins on Microtubules

Kinesin: moves toward plus end
Dynein: moves toward minus end
Both require ATP

Treadmilling

Growth at plus end, shrinkage at minus end
Powers intracellular movement

Dynamic Instability

Rapid switching between growth and shrinkage
Unique to microtubules

Intermediate Filaments

Rope-like structure
No polarity
No motor proteins
Provide tensile strength

Centrioles

Centrioles are not doublet structures