Chapter 2 Objectives

The lipid bilayer:

In aqueous environments, phospholipids spontaneously arrange themselves into two parallel sheets or leaflets that face each other tail-to-tail

Amphipathic nature

hydrophilic head and hydrophobic tails

Hydrophilic Heads:

The highly water-soluble polar head groups face outward to interact with the aqueous extracellular and cytoplasmic environments

Hydrophobic tails

The nonpolar fatty acid acyl chains avoid water and cluster on the inside of the bilayer

membrane permeability

This hydrophobic core makes the membrane highly impermeable to water-soluble molecules and large molecules like proteins, nucleic acids, sugars, and nucleotides. However, small uncharged polar molecules (such as O2, CO2, NH3, and water) can cross fairly freely by traversing transient cracks that open between the hydrophobic tails9.

How does is the rate of diffusion determined within the membrane

specific lipid composition, short or kinked fatty acid chains, for example, increase bilayer permeability

What are the three classes of lipids that make up the membrane

glycerol-based phospholipids, sphingolipids, and cholesterol

Chemical structure of glycerol-based phospholipids

These feature a glycerol backbone where two of the hydroxyl groups are esterified to hydrophobic fatty acid (acyl) chains, and the third hydroxyl group is esterified to a phosphate group. This phosphate group is subsequently esterified to a small hydrophilic molecule, or head group, which determines the specific properties and name of the phospholipid.

Tails saturation of a glycerol-based phospholipid

The acyl groups can vary in carbon length and double bonds. In animal cell membranes, phospholipids characteristically possess one saturated and one unsaturated fatty acid tail.

What are the major types of phospholipids

phosphatidylcholines, phosphatidylethanolamines, phosphatidylserines, and phosphatidylinositols

chemical structure of sphingolipids

These constitute the second major class of membrane lipids and are derivatives of sphingosine

examples of sphingolipids

sphingomyelins, glycosphingolipids, and gangliosides

what is cholestrol

An abundant and chemically distinct lipid interspersed within the bilayer

what is the important roles of phospholipid head groups

negatively or positively charged to determine the electrostatic surface charge of biological membranes

what is the mobility of phospholipids

move laterally, rotate, and flex, rarley do they flip to the other leaflets

what is the lateral and rotational movement

Within the plane of a single leaflet, lipid molecules are highly dynamic—they easily rotate, flex, and diffuse laterally

what is the flip-flop resitriction

Lipids almost never migrate or "flip-flop" from one leaflet to the opposite leaflet because moving a hydrophilic head group through the hydrophobic core carries an extremely high energetic cost

What is the chlosterol exception in mobility within the membrane lipid bilayers

Because cholesterol possesses only a single, small polar hydroxyl group, the energetic cost to cross the membrane is minimal. Consequently, cholesterol can easily flip-flop between leaflets.

The cytoplasmic leaflets characterisitics (intracellular)

Faces the cytoplasm and is predominantly enriched with phosphatidylethanolamine and phosphatidylserine. It also contains phosphatidylinositols, which give rise to phosphoinositides that govern organelle identity, trafficking, and intracellular signaling cascades.

The extracellular leaflet

Faces the extracellular space and is composed primarily of phosphatidylcholine

What does cholestrol aid in

stiffening the membrane

What are the four subtypes of integral membrane proteins

integral monotopic proteins, bitopic (single-pass transmembrane) proteins, polytopic (multi-pass transmembrane) proteins, and lipid-anchored proteins

integral monotopic proteins

• Embedded in only one leaflet of the lipid bilayer.

• Do not span all the way across to the other side.

• Interact with just the inner or outer surface

bitopic (single-pass transmembrane) proteins

• Span the entire lipid bilayer exactly once.

• Have functional segments exposed on both the extracellular and intracellular sides.

  • Further categorized by orientation (such as Type I with an extracellular N-terminus or Type II with an intracellular N-terminus)

polytopic (multi-pass transmembrane) proteins

• Span the membrane multiple times, weaving back and forth across the bilayer.

• Form core structural motifs like multiple hydrophobic alpha helices or beta-barrels.

  • Include essential functional proteins like G-protein coupled receptors and ion channels

lipid-anchored proteins

• Bound covalently to lipid molecules (such as GPI anchors or fatty acid chains) embedded inside the membrane.

• The protein chain itself does not directly enter the hydrophobic core of the bilayer.

within the lipid-anchored proteins, direct lipid-linked proteins are

• associate with the cytoplasmic (intracellular) surface of the plasma membrane

• anchored to the membrane via a covalent attachment to a fatty acid (like myristyl group or a prenyl group)

• acts a hydrophobic tail and is involved with intracellular signaling pathways, carrying messages from cell-surface receptors to effector machinery

within lipid achored proteins, glycophospholipid-linked proteins are

These proteins are anchored to the membrane via a covalent attachment to a glycophospholipid within the membrane

• very often linked to glycosylphosphatidylinositol (GPI) on the outer leaflets of the membrane.

what are the five major functions of membrane proteins

receptors (intracellular signaling), cell-to matrix adhesion, cell-to-cell adhesion, tranposrt proteins (pores, channels, carriers, and pumps), and enzymes

Receptors (Intracellular Signaling)

• Receptor proteins bind to specific external chemical messengers like hormones, changing shape to trigger intracellular signaling cascades.

• This process lets the outside of the cell talk to the inside of the cell without molecules actually entering.

cell-to-matrix adhesion

is the process where a cell attaches to the extracellular matrix (ECM). The ECM is a supportive network of proteins and sugars outside the cell.

• The Main Protein: Integrins are the primary membrane proteins that handle this connection.

• Inside the Cell: One side of an integrin protein links to the cell's cytoskeleton (the internal network of fibers that gives the cell its shape).

• Outside the Cell: The other side of the integrin protein grips onto ECM proteins like collagen or fibronectin.

• are a large family of transmembrane proteins that link to extracellular matrix components (like fibronectin and laminin) at adhesion plaques. Conformational changes in these integrins are transmitted directly to their cytoplasmic tails, communicating structural and signaling events that play a key role in cell shape, growth, and differentiation.

cell to cell adhesion

• How they work: These membrane molecules act as physical anchors that attach adjacent cells to one another.

• Special proteins called cell adhesion molecules (CAMs) stick out of the cell's outer membrane.

• The Handshake: These proteins latch onto matching proteins on neighboring cells, like two puzzle pieces or a Velcro strip locking together.

• Example: Calcium-dependent cadherins bind cells together, helping to organize the internal cytoplasm and directly control gene expression.

transport proteins (pores, channels, carrier, and pumps)

• How they work: These proteins facilitate the transmembrane movement of water-soluble substances across the hydrophobic lipid bilayer.

• Passive vs. Active: They are split into passive transporters (pores and channels), which allow solutes to flow down their concentration gradients without energy expense, and active transporters (carriers and pumps), which require the expenditure of metabolic energy (via ATP hydrolysis) to drive the "uphill" movement of specific molecules or ions against their gradients.

Enzymes

• How they work: Many integral membrane proteins function directly as enzymes to catalyze chemical reactions at the cell surface.

• Example: Examples include metabolic enzymes embedded in the membranes of specialized cells, such as those in the intestine. Additionally, active ion pumps function as enzymes because they actively catalyze the hydrolysis of ATP to harvest the energy required to drive active transport.

structural characteristics of the nucleus

It is typically the largest organelle in eukaryotic cells and is usually round in shape.

It is enveloped by a double membrane. The outer membrane is studded with ribosomes and is associated with the rough endoplasmic reticulum, while the inner membrane is smooth and faces the interior nucleoplasm.

where is the nuclear pore complex located

The outer and inner membranes meet at nuclear pores to establish the nuclear envelope, regulating transport between the cytoplasm and the nuclear interior.

These pores are the location, which is an intricate matrix composed of several hundred proteins.

how do protein gain entry into the nuclear interior

cytoplasmic proteins must be endowed with a specific nuclear localization sequence (NLS)

critical functions of the nucleus

• It serves to store, replicate, and read the cell's genetic information.

• It maintains, copies, and transcribes DNA, playing a central role in governing gene expression and cell division.

• It allows RNA transcripts to pass out through the nuclear envelope into the cytoplasm for translation.

Structure of lysosomes

These are round, membrane-enclosed digestive vesicles.

The lysosome's limiting outer membrane is embedded with specialized proton pumps. These pumps actively transport protons into the organelle to ensure its interior environment remains extremely acidic, which is necessary to aid in protein hydrolysis

critical function of lysosomes

They act as the cell's digestive center, filled with degradative enzymes designed to break down cellular debris and accumulated waste before it can cause cellular damage or dysfunction.

They receive waste cargo from the exterior of the cell; endocytic vesicles fuse directly with the lysosomal membrane to discharge their contents for degradation.

They mediate autophagy

what autophagy

a process where lysosomes engulf internal cellular fragments, forming membrane-enclosed structures within the lysosomal lumen to recycle components. This autophagic process can be highly stimulated by increased metabolic needs.

structure of the mitochondria

Mitochondria feature a distinct double-membrane structure consisting of an outer membrane and an inner membrane.

This dual-membrane layout creates two separate internal compartments: the intermembrane space (between the two membranes) and the matrix space (inside the inner membrane).

what is the inner membrane of the mitochondria characterized by

folds called cristae, which significantly expand its working surface area.

critical functions of mitochondria

Often referred to as the "powerhouse of the cell," the mitochondrion is the primary site of oxidative, oxygen-dependent energy production.

The highly folded inner membrane houses the proteins that constitute the Electron Transport Chain (ETC).

The ETC functions to generate both pH and voltage gradients across the membrane.

Using the energy harvested from nutrients, the mitochondrion uses these gradients to manufacture ATP from ADP and inorganic phosphate

What are intermediate filaments made of?

Tetramers composed of two coiled dimers.

What is the diameter of intermediate filaments?

8–10 nm

What is the major function of intermediate filaments?

Provide structural resilience, help determine cell shape, and allow cells to withstand mechanical stress.

What cell-to-cell junctions are intermediate filaments associated with?

Desmosomes (macula adherens).

How do intermediate filaments contribute to cell-to-cell adhesion?

Cytosolic anchor proteins connect desmosomal cadherins to the intermediate filament network inside the cell.

Why is the connection between desmosomes and intermediate filaments important?

It mechanically couples neighboring cells, allowing tissues to form a continuous structural sheet that resists physical/mechanical stress.

What are microtubules made of?

Heterodimers of α-tubulin and β-tubulin.

How do α- and β-tubulin form microtubules?

α/β-tubulin heterodimers align linearly to form long protofilaments.

What is the diameter of a microtubule?

25 nm — the thickest cytoskeletal filament.

What are the major structural functions of microtubules?

Help determine cell shape and provide mechanical stability.

How are microtubules involved in intracellular transport?

They act as tracks for the directed movement of organelles and vesicles.

What role do microtubules play during cell division?

They form the mitotic spindle, which separates chromosomes.

What are thin filaments made of?

Globular actin (G-actin) monomers.

How does G-actin form F-actin?

G-actin monomers polymerize and arrange into a double helix, producing fibrous actin (F-actin).

What is the diameter of thin filaments?

5–8 nm — the thinnest cytoskeletal filament.

what is the critical function for thin filaments

crucial for cell to cell anchoring at adhering junctions

At these junctions, transmembrane cadherins are linked on their cytosolic side to a dense network of thin actin filaments via specialized anchor proteins (such as vinculin, catenins, and alpha-actinin).

This connection stabilizes cell-to-cell contacts and anchors the cytoskeleton to regulate tissue tension, loss of this association is linked to tumor cell metastasis

thick filament structure

formed by structural assembly of myosin molecules

diameter of thick filaments

10nm

critical function for thick filaments

They act as contractile motor assemblies that interact directly with thin (actin) filaments to generate mechanical force and movement.

This interaction drives fundamental cellular processes such as muscle contraction, cytokinesis (cell division), and active intracellular cargo transport

Thick filaments assemble into

myosin molecules

soulble secreted proteins synthesized in the rough endoplasmic reticulum

1. released from the cell (like peptides, hormone, antibodies, and enzymes)

2. begin as free ribosomal in the cytosol, contains a N-terminal ER signal sequence

3. SRP (signal recognition particle) recognizes the signal sequence and binds, this pauses translation

4. ribosomes moves to rough ER, SRp directs to the SRP receptor, ribosome attaches to a protein channel called the translocon, SRP release and translation resumes

5. protein enters the ER lumen, Ribosome → translocon → ER lumen, (co-translational translocation)

6. signal sequences is removed, a signal peptide cleaves the ER signal sequence, now completely in the ER lumen as a soluble protein

7. Rough ER—> Golgi—> secretory vesicles—> exocytosis

integral/intrinsic membrane proteins secreted proteins synthesized in the rough endoplasmic reticulum

Begin on free ribosomes → have an ER signal sequence → bind SRP → travel to rough ER → enter a translocon

They contain hydrophobic membrane-spanning sequences that prevent the entire protein from entering the ER lumen.

As the protein is being threaded through the translocon, a hydrophobic stop-transfer sequence enters the channel.

The translocon opens laterally, allowing that hydrophobic α-helix to move into the lipid bilayer.

So instead of the entire protein entering the lumen:

Part of protein → ER lumen
Hydrophobic region → ER membrane
Part of protein → cytosol