Cell Physiology: Overview of Membrane, Cytoskeleton & Junctions

Cell physiology is also known as plasma membrane. The average thickness of the cell membrane is 7.5 nm. Plasma membrane is a lipid bilayer membrane, and the proteins are embedded in these layers. Structure of Phospholipid: a hydrophilic head and two hydrophobic chains.

They align in membranes with polar/hydrophilic heads outward and hydrophobic chains inward. One surface remains in contact with extracellular fluid (ECF) while the other surface is in contact with intracellular fluid (ICF).

Composition of Cell/Plasma Membrane

Lipid (45%)

• Phospholipids >Cholesterol
• Triglyceride is absent in the plasma membrane.
• The predominant phospholipid in plasma membranes is phosphatidylcholine

Protein (55%)

Integral or Intrinsic Membrane protein

• Attached to the lipid bilayer by hydrophobic and Van der Waals forces.

Peripheral or Extrinsic Membrane protein

• It is attached to intrinsic membranes by electrostatic forces and hydrogen bonds.
• It is attached to surface membranes by covalent interactions

Carbohydrates(1-3%)

Present in the form of glycoprotein or glycolipid inside the cell membrane.

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Cell Cytoskeleton

Maintains the size and shape of the biological membrane.

Types of Cell Cytoskeleton

Dynamic Cytoskeleton

Length: Increases or decreases proportionally with growth of the cell membrane

Microtubules (Diameter: 25 nm)

Microfilament (Diameter: 7 nm)

Static Cytoskeleton

Length: It does not change with the growth of the cell.

Intermediate filament (Diameter – 10 nm)

Cytoskeleton Properties and Functions 

Microtubules

• Microtubules consist of small globular tubulin subunits, classified as alpha and beta.
• A total of 13 tubules, alternating between alpha and beta, form the periphery/wall of the microtubules.
• Apart from alpha and beta, gamma-tubulin, present at the level of centrioles, forms a mitotic spindle during cell division.
• Found within cilia and flagella, it plays a role in cell motility.
• It is responsible for the intracellular transport process.
• Cell growth involves the polymerization of alpha and beta tubules, resulting in increased length of the tubule, so called the growing end of microtubules (+ve end).
• Guanosine triphosphate (GTP) serves as the energy source for this polymerization.
• As additional tubules depolymerize from one end, the length of microtubules decreases, so-called as the non-growing end of the microtubule (-ve end).

Microfilament

• Microfilament: Actin is composed of globular subunits and is the most abundant intracellular protein present in the mammalian cell.
• Individual subunits of microfilament are known as (globular) G-actin.
• Multiple G actins attach; they form a long filament, known as (filamentous) F actin.
• F-actin helps in muscle contraction as well.
• Two F actin intertwine to form one microfilament.
• As it is a part of the dynamic cytoskeleton, the end that grows because of polymerisation is called the positive end of the microfilament. The other end that does not grow in length is called the negative end of the microfilament.

Intermediate Filament

• It is a fixed structure and is not composed of subunits. 
• It does not change during proliferation of the cell; hence, it is used as a cell marker for the identification of different types of cells.

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Drugs and Cytoskeleton

• Colchicine and vinblastine act on microtubules, preventing their assembly and leading to the death of the cell.
• Paclitaxel (Taxol) binds to microtubules and makes them rigid so that disassembling is no longer possible. Mitotic spindles are not formed, and the cell dies.

Cell-to-Cell Interactions and Junctions

Cell to Basement Interaction

Hemidesmosomes

• Formed by proteins of the integrin family.
• Connected intracellularly by an intermediate filament.

Focal adhesion

• Formed by proteins of the integrin family
• Connected intracellularly by microfilament.
• It is a labile structure that helps in movement of cells from one place to another

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Structure of Gap Junction

• Difference between the area of two plasma membranes: 20 nm.
• Difference between the area of two plasma membranes in close contact with the gap junction: 3.5 nm.
• Connexon protein consists of two hemiconnexon molecules that combine to form a complete gap junction.
• One hemiconnexon protein consists of six subunits, which are called connexin molecules.
• One connexin molecule is composed of four membrane-spanning domains.
• In mutation of connexon molecules, gap junction becomes dysfunctional, and no cell-to-cell interaction takes place, which can lead to several diseases.

Connexins in disease

Mutations of connexin are responsible for ~ 20 different human diseases.

• Clouston syndrome (a connexin 30 defect)- ectodermal dysplasia
• Erythro-keratoderma variabilis (Cx 30.3 and Cx31)
• Cataract (Cx46 and Cx50)
• Idiopathic atrial fibrillation (Cx40)
• X-linked Charcot-Marie-Toth disease (Cx32)

Intercellular Junctions

Tight junction, adherent junction, and desmosome together combine to form a junctional complex.

Points to remember

• In biological membranes, the protein:lipid ratio is equal to 1:1.
• This ratio is not equal for every biological membrane. In certain membranes, the protein ratio is very high.
• The predominant phospholipid in plasma membranes is phosphatidylcholine
• No molecule can pass through a tight junction, adherent junction, or desmosome.

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Important questions               

Q. In which biological membrane is the protein-to-lipid ratio is maximum?

Ans.

• Inner mitochondrial membrane, as it contains all the proteins of the electron transport chain. Ratio is 3:2.
• Sarcoplasmic reticulum (SR) also contains a lot of proteins in the form of channels and pumps.
• Ratio is 2.

Q. In which biological membrane protein-to-lipid ratio is the minimum?

Ans. Myelin sheath contains a high amount of lipid, ratio is equal to 0.23.

Q. What is the role of cholesterol in transition temperature?

Ans.

• If temp < Tm, the fluidity of the membrane increases.
• If temp > Tm, the fluidity of the membrane decreases.

Important MCQs

Q. Plasma membrane is mainly composed of?

1. Cholesterol
2. Carbohydrate
3. Phospholipid
4. Protein

Q. Cell shape and motility is provided by?

1. Centrosomes
2. Microtubules
3. Golgi apparatus
4. Actin

Q. The cell junctions allowing exchange of cytoplasmic molecules between two cells is called?

1. Gap junction
2. Tight junction
3. Focal adhesion
4. Desmosomes

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