Fundamentals

Cell biology is the study of cell structure and function. It helps in the understanding of disease processes as every disease ultimately starts at the cellular level. The ever evolving knowledge of cell biology can be utilized to develop more effective, personalized and safer therapies. A human cell is composed of the nucleus, cytoplasm that contains organelles and a cell membrane that surrounds it.

1. Cell or plasma membrane: It is a double layer of phospholipid molecules interspersed with protein molecules that provide structural support, help in cell-to-cell adhesion, form channels for passage of materials, act as receptor sites and function as carrier molecules. The phospholipid bi-layer has a hydrophobic core and hydrophilic ends and forms an effective diffusion barrier. Cell membranes contain a mix of saturated and unsaturated phospholipids, with the latter type making the cell membrane more fluid at body temperatures. Cell membranes differ in the types of phospholipids. The cell membrane acts as a barrier separating the intracellular from extracellular components, maintains the integrity of a cell, maintains ion gradients and controls passage of materials into and out of the cell. The intracellular environment or cytosol is electronegative compared to the external environment. Ion gradients are essential for transmission of signals like in the nerves and conducting tissues of the heart and to regulate the activity of intracellular enzymes.

Cell membrane associated proteins can be either integral or peripheral. Integral proteins are permanently embedded in the membrane and they form channels, receptors and adhesion molecules. Peripheral proteins are transiently attached to the cell membrane and provide structural support, transmit cellular signals and help with secretory function.

Important features of cell organelles

Ribosomes

• Made of RNA and proteins; consist of small or 40 S and large or 60 S subunits; 40S bind to mRNA and tRNA; 60S has peptidyl transferase activity; Site of translation; String of ribosomes is polysome and are actively involved in protein synthesis; Stain cytoplasm blue/basophilic with H and E stain; Free, cytosolic ribosomes synthesize intracellular or cytosolic proteins.

Rough endoplasmic reticulum or RER

• Studded with ribosomes; Continuous with the SER; Site of synthesis of secretory protein like lysosomal and cell membrane proteins; Cells with increased protein synthesis will have more RER.

Smooth endoplasmic reticulum or SER

• No ribosomes; Role in lipid and steroid biosynthesis and detoxification; Site of cytochrome P450 enzymes , glucuronyl transferase and glucose-6-phosphatase; Modification is sarcoplasmic reticulum in muscle cells.

Golgi apparatus/complex/body

• Located close to the nucleus; Contains multiple stacks of membrane-bound cisternae or sacs enclosing lumens; Has two faces - cis that is receiving face and trans which is exit or releasing face; Acts as packaging and distribution unit; Site of post-translational modifications and recycling; Secretory proteins are packaged into clathrin -coated vesicles; Cell membrane proteins are packaged into non-clathrin coated vesicles.

Lysosomes

• Cytoplasmic vesicles with acidic internal pH; Primary lysosomes are produced by the Golgi; Fuse with phagosomes or pinosomes to form secondary lysosomes; Contain hydrolytic enzymes like acid hydrolases acting as proteases, nucleases and lipases; Role is autophagy, breakdown of phagocytosed substances and processing of exogenous proteins to be presented with class II MHC.

Peroxisomes

• Derived from RER; Produce hydrogen peroxide; Contain catalase and peroxidases; Site of beta oxidation of long chain (> 20 carbon) fatty acids; Secondary site of alcohol detoxification.

Mitochondria

• Site of ATP synthesis, TCA cycle, beta oxidation of fatty acids, oxidative phosphorylation and acetyl-CoA formation; Composed of outer membrane, inner, folded membrane forming cristae, intermembranous space and innermost matrix; ETC or electron transport chain is located in the inner membrane.