Cell Structure and Function: Human Cells

• Cells are the structural and functional units of life
• Organismal functions depend on individual and collective cell functions
• Biochemical activities are dictated by shapes/forms and specific sub-cellular structures of cells
• Continuity of life has a cellular basis, every cell arises from pre-existing cells

Cell Diversity

• Over 200 different types of human cells, differing in size, shape, components, and functions

Generalized Cell

• All cells share common structures and functions
• Human cells have three basic parts: plasma membrane, cytoplasm, and nucleus

Plasma Membrane

• Flexible outer boundary made of a lipid bilayer and proteins in a fluid mosaic
• Plays a dynamic role in cellular activity
• Separates intracellular fluid (ICF) from extracellular fluid (ECF)
• Interstitial fluid (IF) is the ECF that surrounds cells

Membrane Lipids

• The lipid bilayer contains 75% phospholipids
• Phospholipid phosphate heads are polar and hydrophilic
• Phospholipid fatty acid tails are nonpolar and hydrophobic
• The lipid bilayer contains 5% glycolipids
• Glycolipids have polar sugar groups on the outer membrane surface
• The lipid bilayer contains 20% cholesterol
• Cholesterol increases membrane stability

Membrane Proteins

• Membrane proteins allow communication with the environment
• Membrane proteins make up half the mass of the plasma membrane
• Membrane proteins are the most specialized membrane functions
• Some membrane proteins float freely, others are tethered to intracellular structures
• The two types of membrane proteins are integral and peripheral proteins

Integral Proteins

• Integral proteins are firmly inserted into the membrane and are mostly transmembrane
• Integral proteins contain hydrophobic and hydrophilic regions, can interact with lipid tails and water
• Function as transport proteins (channels and carriers), enzymes, or receptors

Peripheral proteins

• Peripheral proteins are loosely attached to integral proteins
• Peripheral proteins include filaments on the intracellular surface for membrane support
• Peripheral proteins function as enzymes or motor proteins for shape change during cell division and muscle contraction, including cell-to-cell connections

Six Functions of Membrane Proteins

• Transport
• Receptors for signal transduction
• Attachment to cytoskeleton and extracellular matrix
• Enzymatic activity
• Intercellular joining
• Cell-cell recognition

Glycocalyx

• The Glycocalyx is the "sugar covering" at the cell surface
• It's made of lipids and proteins with attached carbohydrates (sugar groups)
• Every cell type has a unique pattern of sugars
• It provides specific biological markers for cell-to-cell recognition
• It enables the immune system to recognize "self" and "non-self"
• Cancerous cells change glycocalyx continuously

Cell Junctions

• Some cells are "free" such as blood and sperm cells
• Some cells are bound into communities
• Cells are bound together in three ways: tight junctions, desmosomes, and gap junctions

Tight Junctions

• Adjacent integral proteins fuse to form an impermeable junction encircling the cell
• They prevent fluids and molecules from moving between cells

Desmosomes

• Desmosomes are "rivets" or "spot-welds" that anchor cells together at plaques, which are thickenings on the plasma membrane
• Linker proteins connect plaques between cells
• Keratin filaments extend through the cytosol to the opposite plaque increasing cell stability
• Desmosomes reduce the possibility of tearing

Gap Junctions

• Transmembrane proteins form pores called connexons that allow small molecules to pass from cell to cell
• They facilitate spread of ions, simple sugars, and small molecules between cardiac or smooth muscle cells

Plasma Membrane surrounding cells

• Cells are surrounded by interstitial fluid (IF)
• IF contains thousands of substances including amino acids, sugars, fatty acids, vitamins, hormones, salts, and waste products
• The plasma membrane allows cells to obtain needed substances as well as keeps out what it does not need

Membrane Transport

• Plasma membranes are selectively permeable
• Some molecules pass through easily; others do not
• Substances cross the membrane in two ways: passive and active processes

Types of Membrane Transport

• Passive processes don't require cellular energy (ATP); substance moves down its concentration gradient
• Active processes require energy (ATP) and occur only in living cell membranes

Passive Processes

• Two types of passive transport: diffusion and filtration

Diffusion

• Diffusion is when collisions cause molecules to move down or with their concentration gradient if
  • It is lipid soluble
  • It is small enough to pass through membrane channels
  • It's assisted by a carrier molecule

Simple Diffusion

• Nonpolar lipid-soluble (hydrophobic) substances diffuse directly through the phospholipid bilayer
• Examples include oxygen, carbon dioxide, and fat-soluble vitamins

Facilitated Diffusion

• Certain lipophobic molecules (e.g., glucose, amino acids, and ions) passively trasnport by either
• Binding to protein carriers, or
• Moving through water-filled channels

Carrier-Mediated Facilitated Diffusion

• Transmembrane integral proteins are carriers
• Carriers transport specific polar molecules (e.g., sugars and amino acids) too large for channels
• Binding of substrate causes shape change in carrier and passage across membrane
• Transport is limited by the number of carriers present and carriers become saturated when all are engaged

Channel-Mediated Facilitated Diffusion

• Aqueous channels are formed by transmembrane proteins that selectively transport ions or water
• There are two types of channels: leakage channels, which are always open, and gated channels which are controlled by chemical or electrical signals

Passive Processes: Osmosis

• Osmosis is the movement of solvent (e.g., water) across a selectively permeable membrane
• Water diffuses through plasma membranes in two ways: through the lipid bilayer, or through specific water channels called aquaporins (AQPs)
• Osmosis occurs when water concentration is different on the two sides of a membrane

Osmolarity

• Osmolarity is the measure of the total concentration of solute particles
• Water concentration varies with the number of solute particles because solute particles displace water molecules
• Water moves by osmosis until hydrostatic pressure (back pressure of water on membrane) equals osmotic pressure (tendency of water to move into cell by osmosis)

When solutions of different osmolarity are separated

• If the membrane is permeable to all molecules, both solutes & water cross the membrane until equilibrium is reached
• If the membrane is impermeable to solutes, osmosis occurs until equilibrium is reached

Importance of Osmosis

• Osmosis causes cells to swell and shrink
• Changes in cell volume disrupts cell function, especially in neurons

Tonicity

• Tonicity is the ability of a solution to alter a cell's water volume
• Isotonic solutions have the same non-penetrating solute concentration as cytosol
• Hypertonic solutions have a higher non-penetrating solute concentrations than cytosol
• Hypotonic solutions have a lower non-penetrating solute concentration than cytosol
• Cells have ~0.9% NaCl (salt) so if you place the RBC in more concentrated (hypertonic) solution, the cell will shrink. If you place the RBCs in less concentrated solution (hypotonic), the cell will burst. If you place the cell in isotonic solution, nothing will happen.

Membrane Transport: Active Processes

• Both types of active transport, active and vesicular, require ATP to move solutes across a living plasma membrane, because
  • Solute is too large for channels
  • Solute is not lipid soluble
  • Solute is not able to move down concentration gradient

Active Transport

• Active transport requires carrier proteins (solute pumps) that bind specifically and reversibly with substances
• Active transport moves solutes against the concentration gradient and requires energy
• There are two types: primary and secondary active transport

Primary active transport

• Primary active transport that requires energy directly from ATP hydrolysis
• The energy from hydrolysis of ATP causes shape change in transport protein to "pump" solutes (ions) across membrane

Examples of primary active transport

• Calcium, Hydrogen, Na+-K+ pumps

Sodium-potassium pump

• Na+ and K+ channels allow leakage down concentration gradients
• Sodium-potassium pump (Na+-K+ ATPase) works as an antiporter
• Pumps against Na+ and K+ gradients to maintain high intracellular K+ and high extracellular Na+ concentrations
• Sodium-potassium pump (Na+-K+ ATPase) maintains electrochemical gradients crucial for muscle and nerve function and all cells fluid volume
• It's found in every plasma membrane

Secondary Active Transport

• Secondary active transport requires energy indirectly from ionic gradients created by primary active transport
• Energy stored in ionic gradients is used indirectly to drive transport of other solutes

Cotransport

• Cotransport transports more than one substance at a time
  • Symport system: Substances transported in the same direction
  • Antiport system: Substances transported in opposite directions

Vesicular Transport

• Vesicular transport transports of large particles, macromolecules, and fluids across membrane in membranous sacs called vesicles
• Vesicular transport requires cellular energy (e.g., ATP)

The functions of vesicular transport include

• Exocytosis which transports substances out of the cell
• Endocytosis which transports substances into the cell, e.g. phagocytosis, pinocytosis, receptor-mediated endocytosis
• Transcytosis which transports substances into, across, and then out of a cell
• Vesicular trafficking, which transports substances from one area/organelle to another within a cell

Endocytosis and Transcytosis

• Endocytosis and Transcytosis involve formation of protein-coated vesicles and are receptor mediated and selective
• Some pathogens take advantage of these processes to transport into cells
• Once vesicle is inside cell it may fuse with lysosome or undergo transcytosis

Phagocytosis

• During phagocytosis, pseudopods engulf solids and bring them into the cell's interior
• This forms a vesicle called a phagosome
• Phagocytosis is used by macrophages and some white blood cells
• Macrophages and white blood cells move by amoeboid motion
• Cytoplasm flows into temporary extensions allowing creeping

Pinocytosis

• Pinocytosis is fluid-phase endocytosis
• The plasma membrane infolds, bringing extracellular fluid and dissolved solutes inside the cell
• Fuses with endosome.
• Most cells use pinocytosis to "sample" environment
• It helps with nutrient absorption in the small intestine
• It recycles the membrane components back to the membrane

Receptor-mediated endocytosis

• Aids specific endocytosis and transcytosis
• Cells use this to concentrate materials with limited supply
• Uptake of enzymes, low-density lipoproteins, iron, insulin, and, viruses, diphtheria, and cholera toxins

Clathrin-coated pits

• Clathrin-coated pits is the main route for endocytosis and transcytosis

Exocytosis

• Exocytosis encloses substances enclosed in secretory vesicles for Hormone secretion, neurotransmitter release, mucus secretion, and ejection of wastes

Active Transport and Electrochemical Gradients

• Sodium-potassium (Na+-K+) pump continuously ejects 3Na+ from cell and carries 2K+ in to keep a steady state
• The steady rate is dependent on the rate of Na+ diffusion into cells

Roles of Plasma Membrane Receptors

• Contact signaling involves touching and recognition of other cells
• Contact signaling is key in normal development and immunity
• Chemical signaling involves the interaction between receptors and ligands which includes neurotransmitters, hormones, and paracrines to alter the activity of cell proteins (e.g., enzymes or chemically gated ion channels) - Response is determined by receptor linked to inside cell - A single ligand can cause different cell responses

Cytoplasm

• Found between plasma membrane and nucleus
• Contains cytosol and different cytoplasmic organelles

Cytosol

• Water with solutes (protein, salts, sugars, etc.)

Organelles

• Metabolic machinery of cell; each with specialized function; either membranous or nonmembranous

Inclusions

• Inclusions vary with the cell type
• Examples are glycogen granules, pigments, lipid droplets, vacuoles, and crystals

Membranous Cytoplasmic Organelles

• Include mitochondria, peroxisomes, lysosomes, endoplasmic reticulum, and Golgi apparatus

Nonmembranous Cytoplasmic Organelles

• Include cytoskeleton, centrioles, and ribosomes

Membranes

• Membranes allow crucial compartmentalization

Mitochondria

• Provide most of cell's ATP via aerobic cellular respiration
• Process requires oxygen
• Contains their own DNA, RNA, and ribosomes
• Similar to bacteria and capable of cell division, via fission

Ribosomes

• Granules containing protein and rRNA
• The site of protein synthesis
• Free ribosomes synthesize soluble proteins that function in the cytosol or other organelles
• Membrane-bound ribosomes, forming rough ER, synthesize proteins to be incorporated into membranes, lysosomes, or exported from cell

Endoplasmic Reticulum (ER)

• Interconnected and parallel tubes continuous with outer nuclear membrane
• There are two varieties, rough and smooth ER

Rough ER

• External surface studded with ribosomes
• Manufactures all secreted proteins
• Synthesizes membrane integral proteins and phospholipids
• Assembled proteins move to ER interior, enclosed in vesicle, which go to Golgi apparatus

Smooth ER

• Network of tubules continuous with rough ER
• Its enzymes (integral proteins) function in
  • Lipid metabolism; cholesterol and steroid-based hormone synthesis; making lipids of lipoproteins
  • Absorption, synthesis, and transport of fats
  • Detoxification of drugs, pesticides, and carcinogenic chemicals
  • Converting glycogen to free glucose
  • Storage and release of calcium

Golgi Apparatus

• Stacked and flattened membranous sacs
• Modifies, concentrates, and packages proteins and lipids received from rough ER
• Transport vessels from ER transport proteins modified, tagged for delivery, sorted, and packaged in vesicles

Peroxisomes

• Membranous sacs containing powerful oxidases and catalases
• Detoxify harmful or toxic substances
• Catalyze and synthesize fatty acids
• Neutralize dangerous free radicals (highly reactive chemicals with unpaired electrons)

Lysosomes

• Spherical membranous bags containing digestive enzymes (acid hydrolases)
• Are "Safe" sites for intracellular digestion
• Digest ingested bacteria, viruses, food, and toxins
• Degrade nonfunctional organelles
• Destroy cells in injured or non-useful tissue (autolysis)
• Break down bone to release Ca2+

Endomembrane System

• The endomembrane system as a whole produces, degrades, stores and exports biological molecules
• The endomembrane system degrades potentially harmful substances
• The endomembrane system includes the ER, golgi apparatus, secretory vesicles, lysosomes, nuclear and plasma membranes

Cytoskeleton

• Elaborate series of rods throughout cytosol; proteins link rods to other cell structures
• There are three types of cytoskeleton: microfilaments, intermediate filaments, and microtubules

Microfilaments

• Thinnest of cytoskeletal elements
• Dynamic strands of protein actin
• Each cell has unique arrangement of strands
• Dense web attached to cytoplasmic side of plasma membrane called a terminal web
• Involved in cell motility, change in shape, and endocytosis/exocytosis

Intermediate Filaments

• Tough, insoluble, ropelike protein fibers
• Resist pulling forces on the cell and attach to desmosomes
• Eg., neurofilaments in nerve, keratin filaments in epithelial cells

Microtubules

• Largest of cytoskeletal elements
• Dynamic hollow tubes
• Composed of protein subunits called tubulins
• Determine overall shape of cell and distribution of organelles
• Mitochondria, lysosomes, and secretory vesicles attach to microtubules

Motor Proteins

• protein complexes that function in motility
• Require ATP to power movement.

Centrosome and Centrioles

• "Cell center" near nucleus
• Generates microtubules; organizes mitotic spindle
• Contains paired centrioles, organelles that are small tubes made of microtubules
• Centrioles form basis of cilia and flagella

Cellular Extensions

• Cilia and flagella are whiplike, motile extensions on surfaces of certain cells
• Both contain microtubules and motor molecules
• Cilia move substances across cell surfaces (eg. respiratory in trachea)
• Longer flagella propel whole cells (tail of sperm)

Nucleus

• Largest organelle, has genetic library with blueprints for nearly all cellular proteins
• Responds to signals; dictates kinds and amounts of proteins synthesized
• Most cells are uninucleate
• Some cells are multinucleate such as skeletal muscle cells or bone destruction cells, some liver cells
• Red blood cells are anucleate
• There are three regions/structures

Nuclear Envelope

• Double-membrane that encloses nucleoplasm
• Outer layer continuous with rough ER and bears ribosomes
• Inner lining (nuclear lamina) maintains shape and is scaffold to organize DNA
• Pores in this structure allow substances to pass to and from the nucleus

Nuclear pore complex

• Nuclear pore complex line pores in the nuclear envelope and regulates transport of large molecules into and out of cell

Nucleoli

• Dark-staining spherical bodies within nucleus
• Involved in rRNA synthesis and ribosome subunit assembly

Chromatin

• Threadlike strands of DNA (30%), histone proteins (60%), and RNA (10%)
• Arranged in fundamental units called nucleosomes
• Histones pack long DNA molecules and are involved in gene regulation
• Condense into barlike bodies called chromosomes when cell starts to divide

Cell Cycle

• Defines changes from formation of cell until it reproduces
• Divided into Interphase and Cell division

Interphase

• The period from cell formation to cell division
• Nuclear material is in the form of chromatin
• Has Three subphases: G1, S, G2

G1 (gap 1) phase

• Involves vigorous growth and metabolism
• Cells that permanently cease dividing said to be in G0 phase

S (synthetic) phase

• The S phase is when DNA replication occurs

G2 (gap 2) phase

• Involves preparation for cell division

DNA Replication

• Prior to cell division, a copy of DNA is made

Steps in DNA replication

• DNA helices separate into replication bubbles with replication forks at each end
• Each strand acts as template for complementary strand
• DNA polymerase (enzyme involved) begins adding nucleotides (G pairs with C and A pairs with T)
• DNA polymerase only works in one direction
• Leading strand is synthesized continuously
• Lagging strand is synthesized discontinuously into segments
• DNA ligase splices short segments of discontinuous strand together
• End result: two identical DNA molecules are formed from originals

Semiconservative replication

• During mitotic cell division one complete copy is given to new cell; one is retained in original cell
• Each DNA is composed of one old and one new strand

Cell Division

• Meiosis is cell division that produces gametes (sperm and egg)
• Mitotic cell division produces clones or genetically identical
• Mitotic cell division is Essential for body growth and tissue repair that occurs continuously in some cells (skin and intestinal lining)
• It's absent in most mature cells of nervous tissue, skeletal muscle, and cardiac muscle, repairs with fibrous tissue

Events Of Cell Division

Mitosis

• Mitosis is the division of the nucleus
• Four stages ensure each cell receives copy of replicated DNA
• Prophase
• Metaphase
• Anaphase
• Telophase

Cytokinesis

• Cytokinesis is the division of the cytoplasm via a cleavage furrow

Prophase

• Chromosomes become visible, each with two chromatids joined at centromere
• Centrosomes separate and migrate toward opposite poles
• Nuclear envelope fragments
• Mitotic spindles and asters form
• Kinetochore microtubules attach to kinetochore of centroMerers and draw them toward equator of cell
• Polar microtubules assist in forcing poles apart

Metaphase

• Centromeres of chromosomes aligned at equator
• Plane midway between poles is called the metaphase plate

Anaphase

• Shortest phase of mitosis
• Centromeres of chromosomes split simultaneously
• Chromosomes (V shaped) are pulled toward poles by motor proteins of kinetochores
• Polar microtubules continue forcing poles apart

Telophase

• The process begins when chromosome movement stops
• Two sets of chromosomes uncoil to form chromatin
• New nuclear membrane forms around each chromatin mass
• Nucleoli reappear
• Spindle disappears

Cytokinesis

• Begins during late anaphase
• Ring of actin microfilaments contracts to form cleavage furrow
• Two daughter cells pinched apart, each containing nucleus identical to original

Protein Synthesis

• DNA is master blueprint for protein synthesis
• Gene defines a segment of DNA with blueprint for one polypeptide
• Triplets (three sequential DNA nitrogen bases) form genetic library
• Bases in DNA are A, G, T, and C
• Each triplet specifies coding for number, kind, and order of amino acids in polypeptide

Role of RNA

• DNA decoding mechanism and messenger
• They're primarily three types all formed on DNA in nucleus - Messenger RNA (mRNA) - Ribosomal RNA (rRNA) - Transfer RNA (tRNA)
• RNA differs from DNA through Uracil is substituted for thymine

Three Main Types of RNA

• Messenger RNA (mRNA) carries instructions for building a polypeptide, from gene in DNA to ribosomes in cytoplasm
• Ribosomal RNA (rRNA) is a structural component of ribosomes that, along with tRNA, helps translate message from mRNA
• Transfer RNAs (tRNAs) bind to amino acids and pair with bases of codons of mRNA at ribosome to begin process of protein synthesis

Protein Synthesis in two steps

• Begins with transcription where DNA information coded in mRNA, followed by Translation
• Translation is where mRNA is decoded to assemble polypeptides

Transcription

• Transcription involves transfers of gene base sequence from DNA to complementary base sequence of mRNA
• Initiation is where RNA polymerase separates DNA strands
• Elongation is where RNA polymerase adds complementary nucleotides
• Termination is based on a signal that indicates "stop"

Translation

• Converts base sequence of nucleic acids into amino acid sequence of proteins
• Involves mRNAs, tRNAs, and rRNAs

Genetic Code

• Each three-base sequence on DNA (triplet) is represented by codon
• Codon: complementary three-base sequence on mRNA
• Some amino acids are represented by more than one codon
• tRNAs binds specific amino acid at one end (stem)
• Anticodon at other end (head) binds mRNA codon at ribosome by hydrogen bonds
  • E.g., if codon = AUA, anticodon = UAU

Sequence of Events in Translation

• Three phases involve ATP, protein factors, and enzymes
• Initiation - Small ribosomal subunit binds to initiator tRNA and mRNA to be decoded; scans for start codon - Large and small ribosomal units attach, forming functional ribosome

Elongation

• Codon recognition - tRNA binds complementary codon
• Peptide bond formation - Amino acid of tRNA nearby is bonded to amino acid of tRNA
• Translocation
• tRNAs move one position
• New amino acids are added by other tRNAs as ribosome moves along mRNA
• Initial portion of mRNA can be "read" by additional ribosomes

Termination

• When stop codon (UGA, UAA, UAG) enters A site a
• Signal is given to end translation
• Polypeptide chain is Released and there is separation of ribosome subunits and degradation of mRNA

Summary: From DNA to Proteins

• Complementary base pairing directs a transfer of genetic information in DNA into the amino acid sequence of protein a. DNA triplets -> mRNA codons b. Complementary base pairing of mRNA codons with tRNA anticodons ensures correct amino acid sequence c. Anticodon sequence is identical to DNA sequence, except for uracil substituted for thymine, finally Protein is processed into functional 3-D structure