Cells: The Living Units: Part A p. 61 3 Cells: The Living Units: Part A p. 61

Cell Theory The cell is the smallest structural and functional living unit Organismal functions depend on individual and collective cell functions Biochemical activities of cells are dictated by their specific subcellular structures Continuity of life has a cellular basis

Cell Diversity Over 200 different types of human cells Types differ in size, shape, subcellular components, and functions

(a) Cells that connect body parts, form linings, or transport gases Erythrocytes Fibroblasts Epithelial cells (a) Cells that connect body parts, form linings, or transport gases Nerve cell Skeletal Muscle cell Smooth muscle cells (e) Cell that gathers information and control body functions (b) Cells that move organs and body parts Sperm Macrophage (f) Cell of reproduction Fat cell (c) Cell that stores nutrients (d) Cell that fights disease Figure 3.1

All cells have some common structures and functions Generalized Cell All cells have some common structures and functions Human cells have three basic parts: Plasma membrane—flexible outer boundary Cytoplasm—intracellular fluid containing organelles Nucleus—control center

Chromatin Nuclear envelope Nucleolus Nucleus Smooth endoplasmic reticulum Plasma membrane Mitochondrion Cytosol Lysosome Centrioles Centrosome matrix Rough endoplasmic reticulum Ribosomes Golgi apparatus Secretion being released from cell by exocytosis Cytoskeletal elements • Microtubule • Intermediate filaments Peroxisome Figure 3.2

Plays a dynamic role in cellular activity Plasma Membrane Bimolecular layer of lipids and proteins in a constantly changing fluid mosaic Plays a dynamic role in cellular activity Separates intracellular fluid (ICF) from extracellular fluid (ECF) Interstitial fluid (IF) = ECF that surrounds cells

Extracellular fluid (watery environment) Cholesterol Polar head of phospholipid molecule Cholesterol Glycolipid Glycoprotein Carbohydrate of glycocalyx Outward- facing layer of phospholipids Integral proteins Filament of cytoskeleton Inward-facing layer of phospholipids Bimolecular lipid layer containing proteins Peripheral proteins Nonpolar tail of phospholipid molecule Cytoplasm (watery environment) Figure 3.3

Membrane Lipids 75% phospholipids (lipid bilayer) 5% glycolipids Phosphate heads: polar and hydrophilic Fatty acid tails: nonpolar and hydrophobic (Review Fig. 2.16b) 5% glycolipids Lipids with polar sugar groups on outer membrane surface 20% cholesterol Increases membrane stability and fluidity

Membrane Proteins Integral proteins Firmly inserted into the membrane (most are transmembrane) Functions: Transport proteins (channels and carriers), enzymes, or receptors PLAY Animation: Transport Proteins

Membrane Proteins Peripheral proteins Loosely attached to integral proteins Include filaments on intracellular surface and glycoproteins (sugar proteins) on extracellular surface Functions: Enzymes, motor proteins, cell-to-cell links, provide support on intracellular surface PLAY Animation: Structural Proteins PLAY Animation: Receptor Proteins

Extracellular fluid (watery environment) Cholesterol Polar head of phospholipid molecule Cholesterol Glycolipid Glycoprotein Carbohydrate of glycocalyx Outward- facing layer of phospholipids Integral proteins Filament of cytoskeleton Inward-facing layer of phospholipids Bimolecular lipid layer containing proteins Peripheral proteins Nonpolar tail of phospholipid molecule Cytoplasm (watery environment) Figure 3.3

Functions of Membrane Proteins Transport Receptors for signal transduction Attachment to cytoskeleton and extracellular matrix

A protein (left) that spans the membrane (a) Transport A protein (left) that spans the membrane may provide a hydrophilic channel across the membrane that is selective for a particular solute. Some transport proteins (right) hydrolyze ATP as an energy source to actively pump substances across the membrane. Figure 3.4a

(b) Receptors for signal transduction Signal A membrane protein exposed to the outside of the cell may have a binding site with a specific shape that fits the shape of a chemical messenger, such as a hormone. The external signal may cause a change in shape in the protein that initiates a chain of chemical reactions in the cell. Receptor Figure 3.4b

(c) Attachment to the cytoskeleton and extracellular matrix (ECM) Elements of the cytoskeleton (cell’s internal supports) and the extracellular matrix (fibers and other substances outside the cell) may be anchored to membrane proteins, which help maintain cell shape and fix the location of certain membrane proteins. Others play a role in cell movement or bind adjacent cells together. Figure 3.4c

Functions of Membrane Proteins Enzymatic activity Intercellular joining Cell-cell recognition video

(d) Enzymatic activity Enzymes A protein built into the membrane may be an enzyme with its active site exposed to substances in the adjacent solution. In some cases, several enzymes in a membrane act as a team that catalyzes sequential steps of a metabolic pathway as indicated (left to right) here. Figure 3.4d

(e) Intercellular joining Membrane proteins of adjacent cells may be hooked together in various kinds of intercellular junctions. Some membrane proteins (CAMs) of this group provide temporary binding sites that guide cell migration and other cell-to-cell interactions. CAMs Figure 3.4e

(f) Cell-cell recognition Some glycoproteins (proteins bonded to short chains of sugars) serve as identification tags that are specifically recognized by other cells. Glycoprotein Figure 3.4f

stop

Membrane Junctions Three types: Tight junction Desmosome Gap junction

Membrane Junctions: Tight Junctions Prevent fluids and most molecules from moving between cells Where might these be useful in the body?

(a) Tight junctions: Impermeable junctions prevent molecules Plasma membranes of adjacent cells Microvilli Intercellular space Basement membrane Interlocking junctional proteins Intercellular space (a) Tight junctions: Impermeable junctions prevent molecules from passing through the intercellular space. Figure 3.5a

Membrane Junctions: Desmosomes “Rivets” or “spot-welds” that anchor cells together Where might these be useful in the body?

(b) Desmosomes: Anchoring junctions bind adjacent cells together Plasma membranes of adjacent cells Microvilli Intercellular space Basement membrane Intercellular space Plaque Intermediate filament (keratin) Linker glycoproteins (cadherins) (b) Desmosomes: Anchoring junctions bind adjacent cells together and help form an internal tension-reducing network of fibers. Figure 3.5b

Membrane Junctions: Gap Junctions Transmembrane proteins form pores that allow small molecules to pass from cell to cell For spread of ions between cardiac or smooth muscle cells

(c) Gap junctions: Communicating junctions allow ions and small mole- Plasma membranes of adjacent cells Microvilli Intercellular space Basement membrane Intercellular space Channel between cells (connexon) (c) Gap junctions: Communicating junctions allow ions and small mole- cules to pass from one cell to the next for intercellular communication. Figure 3.5c

Membrane Transport Plasma membranes are selectively permeable Some molecules easily pass through the membrane; others do not

Types of Membrane Transport Passive processes No cellular energy (ATP) required Substance moves down its concentration gradient Active processes Energy (ATP) required Occurs only in living cell membranes

Passive Processes What determines whether or not a substance can passively permeate a membrane? Lipid solubility of substance Channels of appropriate size Carrier proteins PLAY Animation: Membrane Permeability

Passive Processes Simple diffusion Carrier-mediated facilitated diffusion Channel-mediated facilitated diffusion Osmosis

Passive Processes: Simple Diffusion Nonpolar lipid-soluble (hydrophobic) substances diffuse directly through the phospholipid bilayer PLAY Animation: Diffusion

(a) Simple diffusion of fat-soluble molecules Extracellular fluid Lipid- soluble solutes Cytoplasm (a) Simple diffusion of fat-soluble molecules directly through the phospholipid bilayer Figure 3.7a

Passive Processes: Facilitated Diffusion Certain lipophobic molecules (e.g., glucose, amino acids, and ions) use carrier proteins or channel proteins, both of which: Exhibit specificity (selectivity) Are saturable; rate is determined by number of carriers or channels Can be regulated in terms of activity and quantity

Facilitated Diffusion Using Carrier Proteins Transmembrane integral proteins transport specific polar molecules (e.g., sugars and amino acids) Binding of substrate causes shape change in carrier

(b) Carrier-mediated facilitated diffusion via a protein Lipid-insoluble solutes (such as sugars or amino acids) (b) Carrier-mediated facilitated diffusion via a protein carrier specific for one chemical; binding of substrate causes shape change in transport protein Figure 3.7b

Facilitated Diffusion Using Channel Proteins Aqueous channels formed by transmembrane proteins selectively transport ions or water Two types: Leakage channels Always open Gated channels Controlled by chemical or electrical signals

(c) Channel-mediated facilitated diffusion Small lipid- insoluble solutes (c) Channel-mediated facilitated diffusion through a channel protein; mostly ions selected on basis of size and charge Figure 3.7c

Passive Processes: Osmosis Movement of solvent (water) across a selectively permeable membrane Water diffuses through plasma membranes: Through the lipid bilayer Through water channels called aquaporins (AQPs)

(d) Osmosis, diffusion of a solvent such as Water molecules Lipid billayer Aquaporin (d) Osmosis, diffusion of a solvent such as water through a specific channel protein (aquaporin) or through the lipid bilayer Figure 3.7d

Passive Processes: Osmosis Water concentration is determined by solute concentration because solute particles displace water molecules Osmolarity: The measure of total concentration of solute particles When solutions of different osmolarity are separated by a membrane, osmosis occurs until equilibrium is reached

Solute and water molecules move down their concentration gradients (a) Membrane permeable to both solutes and water Solute and water molecules move down their concentration gradients in opposite directions. Fluid volume remains the same in both compartments. Left compartment: Solution with lower osmolarity Right compartment: Solution with greater osmolarity Both solutions have the same osmolarity: volume unchanged H2O Solute Solute molecules (sugar) Membrane Figure 3.8a

(b) Membrane permeable to water, impermeable to solutes Solute molecules are prevented from moving but water moves by osmosis. Volume increases in the compartment with the higher osmolarity. Both solutions have identical osmolarity, but volume of the solution on the right is greater because only water is free to move Left compartment Right compartment H2O Solute molecules (sugar) Membrane Figure 3.8b

When osmosis occurs, water enters or leaves a cell Importance of Osmosis When osmosis occurs, water enters or leaves a cell Change in cell volume disrupts cell function PLAY Animation: Osmosis

Tonicity Tonicity: The ability of a solution to cause a cell to shrink or swell Isotonic: A solution with the same solute concentration as that of the cytosol Hypertonic: A solution having greater solute concentration than that of the cytosol Hypotonic: A solution having lesser solute concentration than that of the cytosol

Figure 3.9 (a) Isotonic solutions (b) Hypertonic solutions (c) Hypotonic solutions Cells retain their normal size and shape in isotonic solutions (same solute/water concentration as inside cells; water moves in and out). Cells lose water by osmosis and shrink in a hypertonic solution (contains a higher concentration of solutes than are present inside the cells). Cells take on water by osmosis until they become bloated and burst (lyse) in a hypotonic solution (contains a lower concentration of solutes than are present in cells). Figure 3.9

Isotonic Solutions

Hypotonic Solution Water molecules enter the cells faster than they can leave

The concentration of solutes is higher than the concentration of water Hypertonic Solution The concentration of solutes is higher than the concentration of water Water molecules move out of the cell faster than they can enter causing the cell to shrink! Crenation (wrinkling)

Hypertonic Solution

Summary of Passive Processes Energy Source Example Simple diffusion Kinetic energy Movement of O2 through phospholipid bilayer Facilitated diffusion Movement of glucose into cells Osmosis Movement of H2O through phospholipid bilayer or AQPs Also see Table 3.1

Vesicular Transport Transport of large particles, macromolecules, and fluids across plasma membranes Requires cellular energy (e.g., ATP)

Vesicular Transport Functions: Exocytosis—transport out of cell Endocytosis—transport into cell Transcytosis—transport into, across, and then out of cell Substance (vesicular) trafficking—transport from one area or organelle in cell to another

Coated pit ingests substance. Extracellular fluid Plasma membrane 1 Extracellular fluid Plasma membrane Protein coat (typically clathrin) Cytoplasm 2 Protein- coated vesicle detaches. Coat proteins detach and are recycled to plasma membrane. 3 Transport vesicle Endosome Uncoated endocytic vesicle 4 Uncoated vesicle fuses with a sorting vesicle called an endosome. Transport vesicle containing membrane components moves to the plasma membrane for recycling. 5 Lysosome 6 Fused vesicle may (a) fuse with lysosome for digestion of its contents, or (b) deliver its contents to the plasma membrane on the opposite side of the cell (transcytosis). (b) (a) Figure 3.12

Coated pit ingests substance. Extracellular fluid Plasma membrane 1 Extracellular fluid Plasma membrane Protein coat (typically clathrin) Cytoplasm Figure 3.12 step 1

Coated pit ingests substance. Extracellular fluid Plasma membrane 1 Extracellular fluid Plasma membrane Protein coat (typically clathrin) Cytoplasm 2 Protein- coated vesicle detaches. Figure 3.12 step 2

Coated pit ingests substance. Extracellular fluid Plasma membrane 1 Extracellular fluid Plasma membrane Protein coat (typically clathrin) Cytoplasm 2 Protein- coated vesicle detaches. Coat proteins detach and are recycled to plasma membrane. 3 Figure 3.12 step 3

Coated pit ingests substance. Extracellular fluid Plasma membrane 1 Coated pit ingests substance. Extracellular fluid Plasma membrane Protein coat (typically clathrin) Cytoplasm 2 Protein- coated vesicle detaches. 3 Coat proteins detach and are recycled to plasma membrane. Endosome Uncoated endocytic vesicle Uncoated vesicle fuses with a sorting vesicle called an endosome. 4 Figure 3.12 step 4

Coated pit ingests substance. Extracellular fluid Plasma membrane 1 Coated pit ingests substance. Extracellular fluid Plasma membrane Protein coat (typically clathrin) Cytoplasm 2 Protein- coated vesicle detaches. Coat proteins detach and are recycled to plasma membrane. 3 Transport vesicle Endosome Uncoated endocytic vesicle 4 Uncoated vesicle fuses with a sorting vesicle called an endosome. Transport vesicle containing membrane components moves to the plasma membrane for recycling. 5 Figure 3.12 step 5

Coated pit ingests substance. Extracellular fluid Plasma membrane 1 Extracellular fluid Plasma membrane Protein coat (typically clathrin) Cytoplasm 2 Protein- coated vesicle detaches. 3 Coat proteins detach and are recycled to plasma membrane. Transport vesicle Endosome Uncoated endocytic vesicle Uncoated vesicle fuses with a sorting vesicle called an endosome. 4 Transport vesicle containing membrane components moves to the plasma membrane for recycling. 5 Lysosome 6 Fused vesicle may (a) fuse with lysosome for digestion of its contents, or (b) deliver its contents to the plasma membrane on the opposite side of the cell (transcytosis). (b) (a) Figure 3.12 step 6

Endocytosis Phagocytosis—pseudopods engulf solids and bring them into cell’s interior Macrophages and some white blood cells

The cell engulfs a large particle by forming pro- Phagocytosis The cell engulfs a large particle by forming pro- jecting pseudopods (“false feet”) around it and en- closing it within a membrane sac called a phagosome. The phagosome is combined with a lysosome. Undigested contents remain in the vesicle (now called a residual body) or are ejected by exocytosis. Vesicle may or may not be protein- coated but has receptors capable of binding to microorganisms or solid particles. Phagosome Figure 3.13a

Endocytosis Fluid-phase endocytosis (pinocytosis)—plasma membrane infolds, bringing extracellular fluid and solutes into interior of the cell Nutrient absorption in the small intestine

The cell “gulps” drops of extracellular fluid containing (b) Pinocytosis The cell “gulps” drops of extracellular fluid containing solutes into tiny vesicles. No receptors are used, so the process is nonspecific. Most vesicles are protein-coated. Vesicle Figure 3.13b

Endocytosis Receptor-mediated endocytosis—clathrin-coated pits provide main route for endocytosis and transcytosis Uptake of enzymes low-density lipoproteins, iron, and insulin

Extracellular substances bind to specific receptor Receptor-mediated endocytosis Extracellular substances bind to specific receptor proteins in regions of coated pits, enabling the cell to ingest and concentrate specific substances (ligands) in protein-coated vesicles. Ligands may simply be released inside the cell, or combined with a lysosome to digest contents. Receptors are recycled to the plasma membrane in vesicles. Vesicle Receptor recycled to plasma membrane Figure 3.13c

Exocytosis Examples: Hormone secretion Neurotransmitter release Mucus secretion Ejection of wastes

The process of exocytosis The membrane- bound vesicle migrates to the Plasma membrane SNARE (t-SNARE) The process of exocytosis Extracellular fluid Fusion pore formed Secretory vesicle The membrane- bound vesicle migrates to the plasma membrane. 1 Vesicle SNARE (v-SNARE) The vesicle and plasma membrane fuse and a pore opens up. 3 Molecule to be secreted Cytoplasm There, proteins at the vesicle surface (v-SNAREs) bind with t-SNAREs (plasma membrane proteins). 2 Vesicle contents are released to the cell exterior. 4 Fused v- and t-SNAREs Figure 3.14a

Summary of Active Processes Energy Source Example Primary active transport ATP Pumping of ions across membranes Secondary active transport Ion gradient Movement of polar or charged solutes across membranes Exocytosis Secretion of hormones and neurotransmitters Phagocytosis White blood cell phagocytosis Pinocytosis Absorption by intestinal cells Receptor-mediated endocytosis Hormone and cholesterol uptake Also see Table 3.2