By/ Dr. Magda Ibrahim Lecturer of Medical Biochemisrty Biological membranes By/ Dr. Magda Ibrahim Lecturer of Medical Biochemisrty

Describe the composition and architecture of biological membrane. By the end of this chapter, you should be able to : Describe the composition and architecture of biological membrane. Summarize the fluid mosaic model of membrane structure. Explain the inside-outside and regional membrane asymmetry identify the factors which cause and maintain membrane fluidity Identify the diseases related to the membrane

Chemical composition Lipid, protein, CHO Diseases related to membrane Biological membranes Characteristics Chemical composition Lipid, protein, CHO Asymmetry inside-outside Regional Fluid- mosaic model Diseases related to membrane

Characteristics of cell membrane 1- Flexible (permits the shape changes during cell growth and division 2- Enclosed specialized compartments inside the cell ( i.e mitochondria, nucleus) 3- Selective permeability and acts as a barrier to maintain differences in composition between inside and outside. 4- self sealing (ability to break and reseal two membranes as in cell division. 5- Exchange materials with extra cellular environment (exocytosis and endocytosis) and with adjacent cell through gap junction 6- It plays an important role in : Cell-cell interaction Trans-membrane signaling 7-It localize enzymes, it provides energy production as in oxidative phosphorylation. 8-Thermodynamically stable, and metabolically active 9-Changes in membrane structure can affect water balance and ion influx , and may lead to variety of diseases

Plasma membrane (Cell membrane) Separates inside from outside Intracellular fluid (ICF) Inside cells (cellular protoplasm) Extracellular fluid (ECF) Outside cells ECF ICF

Characteristics of cell membrane 1- flexible (permits the shape changes during cell growth and division. 2- Enclosed specialized compartment inside the cell ( i.e mitochondria, nucleus)

3- selective permeability and acts as a barrier to maintain differences in composition between inside and outside. 4- self sealing (ability to break and reseal two membranes as in cell division.

Cell-cell interaction Trans-membrane signaling 5- exchange materials with extra cellular environment (exocytosis and endocytosis) and with adjacent cell through gap junction 6- It plays an important role in : Cell-cell interaction Trans-membrane signaling

8-Thermodynamically stable, and metabolically active 7- It localize enzymes, it provide energy production as in oxidative phosphorylation. 8-Thermodynamically stable, and metabolically active 9-Change in membrane structure can affect water balance and ion influx , and may lead to variety of diseases.

Cell membrane composition Lipid Glycolipid Glycerophospholipids Most common is Phosphatidyl Choline Sphingophospholipids - Second major class Sphingomyelin in myelin sheath Sterols Cholesterol is most common Protein Carbohydrate

Phospholipids bilayer. The cell membrane is formed of Phospholipids bilayer. outside inside

Membrane phospholipids Fatty acid (tails) hydrophobic Phosphate + head group (head) hydrophilic Arranged as a bilayer

Fatty acids in membrane phospholipids Membranes are more tightly and less fluid Membranes are less tightly and more fluid Straight tails of phospholipid Kink at the tail of phospholipid Fatty acids in membrane phospholipids Saturated fatty acids Unsaturated fatty acids (cis form)

Phospholipid bilayer Outer leaflet Inner leaflet polar hydrophilic heads Outer leaflet nonpolar hydrophobic tails polar hydrophilic heads Inner leaflet

Membrane phospholipids A- Types of Glycerophospholipids Phosphatidyl choline (lecithin) Phosphatidyl serine Phosphatidyl Ethanolamine Phosphatidyl inositol

B-Sphingomyelin The backbone is sphingosine

Sphingomyelin Sphingosine = Serine+ fatty acid (palmitate) The backbone is sphingosine Sphingosine = Serine+ fatty acid (palmitate) Ceramide= Sphingosine+ fatty acid Sphingomyelin= ceramide + Phosphocholine

2-Cholesterol - What do you know about cholesterol? The cholesterol content of membranes alters their fluidity. The rigid ring of sterols reduces the freedom of neighboring fatty acid chains to move and so decreases fluidity.

3- Glycolipid Cerebroside= ceramide+ CHO (glucose or galactose) Ganglioside= ceramide+ chain of oligosaccharide+ one or more sialic acid Both of them are present in nervous system. They are responsible to inhibit random cell proliferation and cell adhesion----changes in glycolipids ----cancer

Integral proteins Peripheral proteins - Amphipathic - Embedded in either sides of membrane - Firmly associated with hydrophobic interactions to membrane lipids - So, it can be removed by detergent Peripheral proteins In the inner membrane leaflet They don’t react with membrane phospholipids Not removed by detergent

can be released by salt solution with high ionic con. Integral proteins Globular in shape Peripheral proteins bound to the hydrophilic region of integral protein and head groups of phospholipid by hydrogen bonds and electrostatic interaction can be released by salt solution with high ionic con.

Integral proteins Peripheral proteins It spans the membrane ‘trans membrane proteins They are acting as gate-ways or channels Peripheral proteins - Has asymmetrical distribution They may have enzymatic activity

Integral proteins Peripheral proteins - Amphipathic - Embedded in either sides of membrane - Firmly associated with hydrophobic interactions to membrane lipids - So, it can be removed by detergent Globular in shape They are acting as gate-ways or channels It spans the membrane ‘trans membrane proteins Peripheral proteins In the inner membrane leaflet They don’t react with membrane phospholipids Not removed by detergent bound to the hydrophilic region of integral protein and head groups of phospholipid by hydrogen bonds and electrostatic interaction can be released by salt solution with high ionic con. - Has asymmetrical distribution - They may have enzymatic activity

Biological Membrane

III-Membrane Carbohydrates It is present in the outer surface in the cell membrane. It is attached covalenty to : lipid-----------called glycolipid Protein---------called glycoprotein Types: glucose, galactose, mannose It may act as antigens in case of ABO blood group.

Inside – outside asymmetry Phospholipids Choline containing lipids ( Phosphatidyl choline, sphingomyelin) in the outer leaflet Amino- phospholipids (Phosphatidyl serine& ethanolamine)--------in the inner leaflet Cholesterol is present in large quantity in outside more than inside Proteins Irregular protein distributions Carbohydrates External location of CHO in the form glycolipids and glycoproteins

If phosphatidyl serine is present in the outer surface In platelets during blood clot Mark the cell for destruction by apoptosis

Fluid mosaic model of membrane structure This model stated that membrane protein like icebergs that float in the sea of phospholipids The fluid mosaic model states that a membrane is a fluid structure with a “mosaic” of various proteins embedded in it

Fluid mosaic model of membrane structure More fluidity This temp. called “transition temp.” (Tm) -hydrocarbon chain undergo transition from ordered to disordered state The fluidity of the cell membrane depend on lipid composition The hydrocarbon chains are highly aligned to provide a stiff structure Increase in temp

Fluid mosaic model of membrane structure The longer hydrocarbon chain & saturated FA Less fluidity High Tm Shorter & unsaturated (cis- form) FA More fluidity Low Tm

Increase in memb. fluidity Permeability of water and other hydrophilic molecules Binding of protein to receptor e.g insulin The lateral mobility of integral protein

What are the factors which cause and maintain membrane fluidity? The fluidity of the cell membrane depends on lipids composition of the membrane The longer fatty acid -----less fluidity and increase in Tm. the more saturated fatty acid -----less fluidity and increase in Tm. Increase in unsaturated fatty acid (cis) Increase fluidity and decrease in Tm

Diseases related to biological membrane Cystic fibrosis Mutations in the gene encoding (CFTR) protein-cystic fibrosis transmembrane regulator protein- pulmonary disease with high production of viscous secretions, and pancreatic insufficiency Familial hypercholesterolemia Mutations in the gene encoding LDL receptor Hereditary spherocytosis Mutations in the gene encoding structural protein in the red cell membrane

Transport through cell membranes I- Transport of small molecules II- Transport of large molecules III- Transport of small molecules from one cell to another through intercellular contact

I-Transport of small molecules (1)- simple diffusion (2)- facilitated diffusion (3)- Active transport

Transport of large molecules Moving large molecules into & out of cell through vesicles & vacuoles 1-Exocytosis 2-Endocytosis phagocytosis = “cellular eating” pinocytosis = “cellular drinking”