Department of Kinesiology and Applied Physiology Chapter 3: Cells Overview Plasma membrane: structure Plasma membrane: transport Resting membrane potential Cell-environment interactions Cytoplasm Nucleus Cell growth & reproduction Extracellular materials Developmental aspects Department of Kinesiology and Applied Physiology

Do exercise scientists need to think about cells? Exercise in a Pill “AMPK and PPARδ Agonists Are Exercise Mimetics” AICAR activates intracellular pathways that are also activated by exercise. Mice taking AICAR look like mice on exercise. Mice on AICAR plus exercise are supermice. Department of Kinesiology and Applied Physiology

(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

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

Plasma Membrane Bimolecular layer of lipids and proteins in a constantly changing fluid mosaic Plays a dynamic role in cellular activity Separates intracellular fluid from extracellular fluid Interstitial fluid = 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 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 on extracellular surface Functions: Enzymes, motor proteins, cell-to-cell links, provide support on intracellular surface, and form part of glycocalyx PLAY Animation: Structural Proteins PLAY Animation: Receptor Proteins

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

(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

Membrane Junctions Three types: Tight junction Desmosome Gap junction

(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

(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

(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: How things get in and out of cells 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

(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

(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

(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

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: How much dissolved material there is in a solution. Tonicity determines whether a solution will make cells shrink or swell. Isotonic: A solution with the same solute concentration as the inside of a normal cell Hypertonic: A solution with a greater solute concentration than than a normal cell Hypotonic: A solution with a lesser solute concentration than a normal cell

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

Membrane Transport: Active Processes Two types of active processes: Active transport Vesicular transport Both use ATP to move solutes across a living plasma membrane

Requires carrier proteins (solute pumps) Active Transport Requires carrier proteins (solute pumps) Moves solutes against a concentration gradient Types of active transport: Primary active transport Secondary active transport

Primary Active Transport Energy from breakdown of ATP causes shape change in transport protein to “pump” molecules across the membrane Example: Sodium-potassium pump (Na+-K+ ATPase) Located in all plasma membranes Involved in primary and secondary active transport of nutrients and ions Maintains “electrochemical gradients” essential for functions of muscle and nerve tissues

Figure 3.10 Extracellular fluid Na+ Na+-K+ pump ATP-binding site K+ Na+ bound Cytoplasm 1 Cytoplasmic Na+ binds to pump protein. P ATP K+ released ADP 6 K+ is released from the pump protein and Na+ sites are ready to bind Na+ again. The cycle repeats. 2 Binding of Na+ promotes phosphorylation of the protein by ATP. Na+ released K+ bound P Pi K+ 5 K+ binding triggers release of the phosphate. Pump protein returns to its original conformation. 3 Phosphorylation causes the protein to change shape, expelling Na+ to the outside. P 4 Extracellular K+ binds to pump protein. Figure 3.10

Secondary Active Transport Energy stored in ionic gradients is used indirectly to drive transport of other solutes Always involves cotransport – transport of more than one substance at a time Two substances transported in same direction (Na+, glucose) Two substances transported in opposite directions (Na+, H+) Mod WCR

The ATP-driven Na+-K+ pump stores energy by creating a Extracellular fluid Glucose Na+-glucose symport transporter loading glucose from ECF Na+-glucose symport transporter releasing glucose into the cytoplasm Na+-K+ pump Cytoplasm 1 The ATP-driven Na+-K+ pump stores energy by creating a steep concentration gradient for Na+ entry into the cell. 2 As Na+ diffuses back across the membrane through a membrane cotransporter protein, it drives glucose against its concentration gradient into the cell. (ECF = extracellular fluid) Figure 3.11

Vesicular Transport Transport of large particles, macromolecules, and fluids across plasma membranes Requires cellular energy (e.g., ATP) Functions: Exocytosis—transport out of cell Endocytosis—transport into cell (receptor mediated; phago-; pino-) Transcytosis—transport into, across, and then out of cell Vesicular transport within a cell (see the video) Mod WCR

The cell engulfs a large particle by forming pro- Endocytosis: 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

The cell “gulps” drops of extracellular fluid containing (b) Endocytosis: 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

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 Membrane-bound vesicle migrates to Plasma membrane SNARE (t-SNARE) Extracellular fluid Fusion pore formed Secretory vesicle Membrane-bound vesicle migrates to plasma membrane. 1 Vesicle SNARE (v-SNARE) Vesicle and plasma membrane fuse and pore opens up. 3 Molecule to be secreted Cytoplasm Proteins at vesicle surface (v-SNAREs) bind with t-SNAREs (plasma membrane proteins). 2 Vesicle contents released to 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