Anatomy & Physiology: Biology of the Cell
General Cell Biology Overview
Anatomy & Physiology: Biology of the Cell (Chapter 04)
The Range of Cell Sizes
Unaided Eye:
10 \text{ m} (human height)
1 \text{ m} (some skeletal muscle cells)
0.1 \text{ m} (ostrich egg)
Light Microscope:
1 \text{ mm} (human oocyte)
100 \, \mu \text{m} (most plant and animal cells, average ~$30 \, \mu \text{m}$)
10 \, \mu \text{m} (red blood cell)
1 \, \mu \text{m}} (mitochondrion, most bacteria)
Electron Microscope:
100 \text{ nm} (viruses)
10 \text{ nm} (ribosomes, large biological macromolecules like proteins)
1 \text{ nm} (small molecules like amino acids)
0.1 \text{ nm} (atom)
The Variety of Cell Shapes
Irregular-shaped: Nerve cells
Biconcave disc: Red blood cells
Cube-shaped: Kidney tubule cells
Column-shaped: Intestinal lining cells
Spherical: Cartilage cells
Cylindrical: Skeletal muscle cells
The Structure of a Prototypical Cell
Cytoplasm: Consists of cytosol, organelles, and inclusions.
Cytosol (intracellular fluid): The fluid component of the cytoplasm.
Inclusions: Temporary storage of substances such as glycogen, melanin, or triglycerides.
Nucleus:
Nuclear envelope
Nucleoplasm
Nucleolus
Membrane-Bound Organelles: (These are enclosed by a membrane, often appearing as "dots" in diagrams)
Rough endoplasmic reticulum
Smooth endoplasmic reticulum
Golgi apparatus
Lysosome
Peroxisome
Mitochondrion
Vesicle
Non-Membrane-Bound Organelles: (These do not have a surrounding membrane)
Ribosomes (free and bound)
Centrosome
Proteasomes
Cytoskeleton
Plasma Membrane:
Modifications: Microvilli, Cilia, Flagellum (Note: Not all cells possess all these modifications; e.g., not all cells have a flagellum).
The Cell Cycle
Interphase: The non-dividing phase, approximately 23 hours.
\text{G}_1 phase: Growth and preparation for DNA replication. During this phase, cells differentiate.
S phase: DNA replication occurs, resulting in duplicated chromosomes, each composed of two sister chromatids.
\text{G}_2 phase: Brief phase where the cell grows further and prepares for division. Centriole replication is completed, and enzymes for cell division are synthesized.
Mitotic (M) phase: The dividing phase, approximately 1 hour.
Mitosis: Division of the nucleus, comprising four stages:
Prophase:
First stage of mitosis.
Chromatin supercoils to form visible chromosomes.
Each chromosome consists of two sister chromatids joined at a centromere.
The nucleolus breaks down.
Spindle fibers (microtubules) begin to grow from the centrioles.
Centriole pairs move towards opposite poles of the cell.
The dissolution of the nuclear envelope marks the end of prophase.
Metaphase:
Second stage of mitosis.
Replicated chromosomes align along the equatorial plate (middle) of the cell, forming a single file line.
Spindle fibers extend from the centrioles and attach to the centromere of each chromosome.
Anaphase:
Third stage of mitosis.
Spindle fibers pull sister chromatids apart towards opposite poles.
Each separated chromatid is now considered an individual chromosome (a single DNA double helix with its own centromere), often called a single-stranded chromosome.
Cytokinesis (cleavage furrow formation) often begins during this stage.
Telophase:
Fourth and final stage of mitosis.
Essentially the reverse of prophase.
New nuclear envelopes form around the separated chromosomes at each pole.
Chromosomes uncoil and return to the looser chromatin form.
The nucleoli reappear.
The spindle fibers disassemble and disappear.
Cytokinesis: Division of the cytoplasm.
Often overlaps with anaphase and telophase.
Microfilament proteins at the cell periphery form a contractile ring that creates a cleavage furrow.
This furrow pinches the mother cell into two distinct daughter cells, completing cell division.
Cell Division Types
Mitosis:
Occurs in somatic cells (all cells except sex cells).
One cell divides to produce two genetically identical daughter cells.
Essential for development, tissue growth, replacement of old cells, and tissue repair.
Meiosis:
Occurs in sex cells (cells that give rise to sperm or oocytes).
Produces four haploid cells, each with half the number of chromosomes of the parent cell.
Clinical View: Tumors
Cell division is regulated by complex mechanisms that signal cells to divide or stop dividing.
When cell signaling is disrupted, cells may divide uncontrollably, leading to the formation of tumors.
Tumors interfere with the function of normal surrounding cells.
Tumor cells can become malignant and enter the blood or lymph, spreading to other areas of the body through a process called metastasis.
The Plasma Membrane
Lipid Components of the Plasma Membrane
Phospholipid Bilayer: The fundamental structure, composed of phospholipids with hydrophilic (polar) heads facing the aqueous environment and hydrophobic (nonpolar) tails forming the interior.
Cholesterol:
A four-ring lipid molecule scattered within the phospholipid bilayer.
Function: Strengthens the membrane and stabilizes it against temperature extremes, making it less fluid at higher temperatures and preventing it from solidifying at lower temperatures.
Glycolipids:
Lipids with attached carbohydrate groups.
Location: Primarily on the outer phospholipid region only, contributing to the glycocalyx.
Structure and Functions of the Plasma Membrane
Integral proteins are transverse, meaning they go through both layers. Proteins that go through one layer are called peripheral proteins.
Overall Structure: A fluid mosaic of phospholipids, cholesterol, glycolipids, and various proteins.
Functions:
Physical Barrier: Establishes a flexible boundary between the inside (cytosol) and outside (interstitial fluid) of the cell, providing both support and protection.
Selectively Permeable Boundary: Regulates the movement of substances into and out of the cell through various membrane transport processes, allowing some substances to pass more easily than others.
Electrochemical Gradients: Actively establishes and maintains an electrical charge difference (resting membrane potential) across the plasma membrane, crucial for nerve and muscle function.
Cell Communication: Contains specific receptor proteins that recognize and respond to external signals (ligands), allowing cells to interact with their environment and other cells.
Membrane Proteins
Movement: Proteins float and move within the fluid phospholipid bilayer.
Function: Perform most of the membrane's functions.
Two Structural Types:
Integral Proteins: Embedded within or extend completely through the lipid bilayer; often span the entire membrane (transmembrane proteins).
Peripheral Proteins: Loosely attached to the external or internal surface of the membrane; do not extend through the bilayer.
Functional Categories:
Transport Proteins: Include channels, carriers, and pumps that move substances across the membrane.
Receptor Proteins: Bind specific ligands (e.g., hormones) to initiate a cellular response.
Identity Markers (Glycoproteins): Serve to identify the cell to other cells (e.g., immune system cells).
Enzymes: Catalyze chemical reactions directly at the membrane surface.
Anchoring Sites: Secure the cytoskeleton to the plasma membrane.
Cell-Adhesion Proteins: Facilitate cell-to-cell attachments.
Membrane Transport
Passive Processes
Do not require direct expenditure of cellular energy (ATP).
Substances move down their concentration gradient (from an area of higher concentration to lower).
Diffusion continues until equilibrium is reached.
Diffusion: Movement of solutes.
Simple Diffusion:
Molecules move unassisted directly through the phospholipid bilayer.
Characterized by movement of small, nonpolar solutes (e.g., respiratory gases like O2 and CO2, some fatty acids, ethanol, urea).
Movement rate depends on the steepness of the concentration gradient; a steeper gradient results in a faster rate.
Continues as long as a concentration gradient exists until equilibrium is reached.
Facilitated Diffusion:
Transport process for small charged or polar solutes that cannot cross the lipid bilayer unassisted.
Requires the assistance of specific plasma membrane proteins.
Types:
Channel-Mediated Diffusion: Ions (e.g., Na^+ through Na^+ leak channels, K^+ through K^+ leak channels) move down their concentration gradient through water-filled protein channels. These channels can be leak channels (always open) or gated channels (open/close in response to stimuli).
Carrier-Mediated Diffusion: Small polar molecules (e.g., glucose) are assisted across the membrane by specific carrier proteins. Binding of the substance causes a conformational change in the carrier protein, which then releases the substance on the other side of the membrane. This process moves substances down their concentration gradient.
Transport Maximum (Tm): The maximum rate at which a substance can be transported across the membrane, determined by the number of available channels or carrier proteins.
Osmosis: Movement of water.
Passive movement of water through a selectively permeable membrane (which permits water passage but restricts most solute passage).
Osmosis is promoted by differences in water concentration (which is inversely related to solute concentration) on either side of the membrane.
Water moves from an area of higher water concentration (lower solute concentration) to an area of lower water concentration (higher solute concentration).
Aquaporins: Protein channels that greatly facilitate bulk water transport across the membrane.
Osmotic Pressure: The pressure exerted by the movement of water across a semipermeable membrane due to water concentration differences. A steeper gradient results in more water movement and greater osmotic pressure.
Hydrostatic Pressure: Pressure exerted by a fluid on the inside wall of its container.
Osmosis and Tonicity
Tonicity: Describes the ability of a solution to change the volume or pressure of a cell by osmosis.
Isotonic Solution:
Both the cytosol and the solution have the same relative concentration of solutes.
Example: Normal saline with a concentration of 0.9\% NaCl, commonly used in IV solutions.
Result: No net movement of water; the cell volume remains stable.
Hypotonic Solution:
A solution with a lower concentration of solutes and thus a higher concentration of water than the cytosol.
Example: Erythrocytes in distilled water.
Result: Water moves by osmosis from the solution into the cell, increasing the cell's volume and pressure. This can lead to hemolysis (bursting) of red blood cells.
Hypertonic Solution:
A solution with a higher concentration of solutes and thus a lower concentration of water than the cytosol.
Example: Erythrocytes in 3\% NaCl solution.
Result: Water moves by osmosis from inside the cell to the outside, decreasing the cell's volume and pressure. This causes crenation (shrinking) of red blood cells.
Active Processes
Require the expenditure of cellular energy (ATP).
Involve either the movement of a substance up its concentration gradient (from lower to higher concentration) or the formation/loss of a vesicle.
Active transport mechanisms never reach equilibrium, constantly working to maintain concentration gradients.
Active Transport: Movement of ions or small molecules against their concentration gradient.
Primary Active Transport:
Uses energy directly from the breakdown of ATP.
Involves the phosphorylation of the carrier protein (a phosphate group from ATP is added to it), which causes a conformational change and moves the substance across the membrane.
Sodium-Potassium (Na^+/K^+) Pump: A crucial example.
Net Result: Pumps 3 \text{ Na}^+ ions out of the cell and 2 \text{ K}^+ ions into the cell for each ATP molecule hydrolyzed.
Mechanism:
Three Na^+ ions from the cytosol bind to the pump, along with ATP.
ATP is hydrolyzed, and the phosphate group (P_i) attaches to the pump, causing it to change shape and release the three Na^+ ions into the interstitial fluid.
Two K^+ ions from the interstitial fluid bind to new sites on the pump, and the P_i is released.
The pump reverts to its original shape, releasing the two K^+ ions into the cytosol.
Significance: Maintains the electrochemical gradient (resting membrane potential) across the plasma membrane, essential for nerve impulse transmission and muscle contraction.
Secondary Active Transport:
Does not directly use ATP.
Energy source is the established electrochemical gradient of another substance (often Na^+) that was created by primary active transport.
Symport (Cotransport): Two substances move in the same direction across the membrane.
Antiport (Countertransport): Two substances move in opposite directions across the membrane.
Vesicular Transport (Bulk Transport):
Involves the transport of large substances across the plasma membrane enclosed within a membrane-bounded sac called a vesicle.
Requires ATP.
Exocytosis:
Process by which large substances are secreted from the cell.
Material (macromolecules too large for other transport methods) is packed into intracellular transport vesicles.
The vesicle membrane fuses with the plasma membrane, releasing its contents into the interstitial fluid outside the cell.
Vesicle membrane components are integrated into the plasma membrane.
Example: Release of neurotransmitters from nerve cells.
Endocytosis:
Process by which materials are brought into a cell via the formation of a vesicle.
Requires ATP.
Three types of Endocytosis:
Phagocytosis (Cellular Eating): The cell engulfs a large particle (e.g., bacterium, cell debris) external to the cell by extending pseudopodia around it, forming a membrane sac (phagosome). The phagosome is internalized, and its contents are digested after fusing with a lysosome. Performed by a few specialized cell types (e.g., white blood cells).
Pinocytosis (Cellular Drinking): The cell internalizes droplets of interstitial fluid containing dissolved solutes by forming multiple, small vesicles. This is a common process performed by most cells.
Receptor-Mediated Endocytosis: Uses specific receptors on the plasma membrane to bind particular molecules (ligands) within the interstitial fluid. These ligand-receptor complexes cluster in membrane regions called clathrin-coated pits, which then invaginate and form clathrin-coated vesicles. This enables the cell to obtain bulk quantities of specific substances efficiently (e.g., transport of cholesterol from blood into a cell).
Electrochemical Gradient and the Resting Membrane Potential (RMP)
The plasma membrane establishes and maintains an electrochemical gradient across itself.
This gradient is directly related to the Resting Membrane Potential (RMP).
The RMP is essential for the proper function of excitable cells, such as muscle cells and nerve cells.
Characteristics of RMP:
The RMP is the electrical potential difference across the plasma membrane when the cell is at rest (not actively transmitting signals).
Typically ranges from -50 \text{ mV} to -100 \text{ mV} in most cells, with the inside of the cell being more negative relative to the outside (e.g., -70 \text{ mV}).
Ion Distribution:
Interstitial Fluid (outside the cell): Higher concentration of Na^+ ions.
Cytosol (inside the cell): Higher concentration of K^+ ions and negatively charged proteins (\text{A}^-).
Factors Establishing and Maintaining RMP:
Na^+/K^+ Pump: Actively pumps 3 \text{ Na}^+ out and 2 \text{ K}^+ in, contributing to the negative charge inside the cell.
Leak Channels: More K^+ leak channels are present than Na^+ leak channels, allowing more K^+ to diffuse out of the cell than Na^+ to diffuse in. Since K^+ is positively charged, its efflux makes the inside more negative.
Negatively Charged Proteins: Large, non-diffusible negatively charged proteins are trapped inside the cell, further contributing to the negative RMP.
Cellular Structures (Organelles)
Membrane-Bound Organelles
The Endoplasmic Reticulum (ER): A network of interconnected membranes that form flattened sacs (cisternae) and tubules.
Rough Endoplasmic Reticulum (Rough ER):
Has ribosomes attached to its external surface, giving it a "rough" appearance.
Functions:
Protein Synthesis: Synthesizes proteins destined for secretion, incorporation into the plasma membrane, or as enzymes within lysosomes.
Protein Processing & Storage: Modifies newly synthesized proteins (e.g., by adding carbohydrates to form glycoproteins), folds them correctly, and stores them. Proteins are tagged for appropriate shipping.
Organelle Formation: Helps in the formation of peroxisomes.
Vesicle Formation: Forms transport vesicles to package and ship proteins to the Golgi apparatus.
Smooth Endoplasmic Reticulum (Smooth ER):
Lacks ribosomes, giving it a "smooth" appearance.
Functions:
Lipid Synthesis: Site of various lipid synthesis, including steroid hormones (e.g., in reproductive organs) and phospholipids.
Carbohydrate Metabolism: Involved in glycogen synthesis and breakdown (e.g., in liver cells).
Detoxification: Detoxifies drugs, alcohol, and poisons (especially abundant in liver cells).
Vesicle Formation: Forms transport vesicles for shipping lipids and other molecules to the Golgi apparatus.
Golgi Apparatus: Composed of stacks of flattened, membranous sacs called cisternae.
Functions: Modification, packaging, and sorting center for proteins and lipids received from the ER.
Synthesis: Forms proteoglycans.
Processing & Storage: Further modifies and stores proteins and lipids (e.g., addition or removal of carbohydrate groups).
Organelle Formation: Synthesizes lysosomes.
Vesicle Formation: Forms various secretory vesicles that:
Deliver components to the plasma membrane.
Release contents from the cell via exocytosis.
Provide digestive enzymes to lysosomes.
Endomembrane System: A comprehensive system that coordinates the synthesis, modification, and shipping of proteins and lipids into, out of, and within a cell. It includes the nuclear envelope, ER, Golgi apparatus, lysosomes, peroxisomes, and plasma membrane.
Proteins synthesized in the rough ER are released in transport vesicles.
These vesicles move and fuse with the cis-face (receiving side) of the Golgi apparatus.
Proteins are then modified as they move through the Golgi cisternae.
Modified proteins are packaged into secretory vesicles that bud off from the trans-face (shipping side) of the Golgi.
These secretory vesicles can either:
Merge with the plasma membrane to insert their contents (e.g., membrane proteins).
Release their contents outside the cell via exocytosis.
Deliver digestive enzymes to lysosomes.
Vesicles resulting from endocytosis also fuse with lysosomes for digestion of their contents.
Lysosomes: Membrane-bound sacs containing powerful digestive enzymes.
Functions:
Digestion: Break down cellular waste products, macromolecules, and foreign invaders (bacteria).
Autophagy: Digest and recycle old or damaged organelles.
Autolysis: Self-destruction of the cell (e.g., during development or in damaged cells).
Clinical View: Lysosomal Storage Diseases:
A group of heritable disorders caused by mutations in genes for lysosomal enzymes, leading to the accumulation of incompletely digested molecules within lysosomes.
Example: Tay-Sachs disease: Individuals lack a specific enzyme needed to break down complex membrane lipids. These lipids accumulate within nerve cells, leading to symptoms like paralysis, visual impairment, hearing loss, and ultimately death by age 4.
Peroxisomes: Small, spherical membrane-bound organelles.
Pinched off from the rough ER, they incorporate proteins that serve as their enzymes.
Metabolic Functions: Primarily involve reactions that produce hydrogen peroxide (H2O2).
Digestion: Break down various molecules (e.g., fatty acids via beta-oxidation, amino acids, uric acid) using hydrogen peroxide.
Detoxification: Detoxify harmful substances by converting them into less toxic forms (e.g., alcohol in the liver).
Synthesis: Form specific types of lipids (e.g., plasmalogens and bile salts).
Mitochondria: The "powerhouses" of the cell, responsible for generating most of the cell's supply of ATP.
Structure: Double-membraned organelle; inner membrane is extensively folded into cristae to increase surface area for ATP synthesis.
Function: Site of cellular respiration, producing ATP through oxidative phosphorylation.
Non-Membrane-Bound Organelles
Ribosomes: Small complexes of ribosomal RNA (rRNA) and protein.
Functions: Perform protein synthesis (translation).
Bound Ribosomes: Attached to the external surface of the ER membrane.
Synthesize proteins destined to be incorporated into the plasma membrane, exported from the cell, or housed within lysosomes.
Free Ribosomes: Suspended within the cytosol.
Synthesize all other proteins for use within the cell (e.g., enzymes of the cytosol).
Centrosome: A region located near the nucleus in animal cells.
Structure: Consists of a pair of perpendicularly oriented cylindrical centrioles (each composed of nine triplets of microtubules) surrounded by amorphous protein called the pericentriolar material.
Functions:
Microtubule Organization: Organizes microtubules within the cytoskeleton and supports their growth in non-dividing cells.
Cell Division: Acts as the main microtubule-organizing center (MTOC); organizes microtubules to form the spindle fibers during cellular division, which are crucial for chromosome separation.
Proteasomes: Large, barrel-shaped protein complexes.
Functions: Degrade unwanted or improperly folded proteins (via ubiquitination) into small peptides, which can then be recycled.
Cytoskeleton: A network of protein filaments and tubules throughout the cell's cytoplasm.
Components and Associated Proteins:
Microfilaments (Actin Filaments): Small, thin protein filaments composed of actin.
Intermediate Filaments: Ropelike protein fibers, more stable than microfilaments and microtubules.
Microtubules (Tubulin Filaments): Large, hollow cylinders composed of tubulin protein.
Functions:
Structural Support & Organization: Maintains cell shape, organizes organelles within the cell (all cytoskeleton proteins). Microfilaments provide internal support to the plasma membrane and microvilli. Intermediate filaments stabilize desmosome cell junctions.
Cell Division: Microtubules separate chromosomes during cell division. Microfilaments form the cleavage furrow that splits the cell into two daughter cells during cytokinesis.
Movement: Microfilaments facilitate cytoplasmic streaming and participate in muscle contraction. Microtubules serve as tracks for the movement of organelles and vesicles. Microtubules are also the contractile proteins of cilia and flagella.
Structures of the Cell's External Surface
Cilia:
Hairlike projections extending from the cell surface.
Contain supportive microtubules arranged in a 9+2 pattern.
Function: Beat rhythmically to move substances (e.g., mucus, fluid) along the cell surface (e.g., in the respiratory tract).
Flagella:
Similar basic structure to cilia but are much longer and wider.
Function: Propel the entire cell (e.g., the tail of a sperm cell).
Microvilli:
Minute, fingerlike extensions of the plasma membrane.
Supported by actin microfilaments within their core.
Function: Greatly increase the surface area of the cell for absorption and secretion (e.g., in intestinal lining cells).
Membrane Junctions
Specialized contact points between adjacent cells that link them together.
Tight Junctions:
Formed by fusion of integral proteins in adjacent plasma membranes.
Function: Create a virtually impermeable barrier that prevents substances from passing between cells (e.g., in the lining of the stomach and intestines to prevent leakage).
Gap Junctions:
Consist of connexons (protein channels) that bridge the intercellular space between adjacent cells.
Function: Allow direct, rapid passage of small molecules and ions between cells, facilitating intercellular communication (e.g., in cardiac muscle for synchronized contraction).
Desmosomes:
Function: Provide strong mechanical adhesion between cells, acting like