Biomembranes separate cell interiors from the external environment, participate in cell functions, and mediate cell-cell and cell-environment interactions. Biomembranes are composed of a phospholipid bilayer with embedded and peripheral proteins. The phospholipid bilayer forms a semipermeable barrier through self-assembly of phospholipid molecules with hydrophobic tails and hydrophilic heads. Membrane proteins have hydrophobic regions that extend through the bilayer and hydrophilic regions exposed to the aqueous environment on either side. Additional structures like the glycocalyx, extracellular matrix, basal lamina, and focal adhesions further facilitate cellular interactions and processes like migration.

1. Membrane structure and mechanisms of cell adhesion and locomotion

2.  Separate the cell interior from an external environment  Take part in cell functions  Partition the c y toplasm into compartments - organelles  Mediate contacts with other cells or surrounding environment  Create a semipermeable barrier – impermeable for macromolecules and selectively permeable for ions Biomembranes

3. Biomembr anes Development of membrane concept 1890 : cell surface is of lipidic nature (Overton) 1926 : cellular membranes consist of lipid bilayers (Gorder and Grendel) 1943: the surface of lipid bilayer is coated by proteins (Davson and Danielli) 1960: unit membrane (Robertson) 1972: fluid mosaic model (Singer a Nicholson) 1980: detailed structure of membrane proteins (Unwin a Henderson)

4. Chemical composition of membranes membrane lipids phospholipids, sfingolipids , sterols membrane proteins (glycoproteins) Phospholipids: ( phosphoglycerides ) phosphatidyl- cholin ethanolamine serine inositol Sphingolipids -sfingosin Sterols cholesterol ergosterol

5. Physical features of biomembranes Stabili ty of the bila y er :  facilitated by hydrophobic interaction between fatty acid chains  unsaturated fatty acids decrease the bilayer stability  Sterols increase the bilayer stability Polarity of phospholipids hydrophilic ends (PO 4 , , COOH, OH, NH 3 hydrophobic ends fatty acid chains Self-assembly into bilayers liposomes , myeline structures Lipid asymmetry Membrane fluidity

6. Mobility of membrane phospholipids Membrane fluidity rotation lateral migration flip-flop – transversal diffusion transition point

7. Heterogeneity of membrane lipids and their asymmetric distribution in bilayer. Rafts: small islands of sphingolipids and cholesterol creating a separate phase (50 nm in diameter) in outer leaflet of plasma membrane

8. Membrane proteins - enzymes - receptor proteins - transport proteins (pumps,carriers, channels) - linkers Association of membrane proteins with the lipid bilayer

9. Membrane proteins: - have both hydrophobic and hydrophilic regions - the hydrophobic region extend through the bilayer and is formed by hydrophobic amino acids hydrophilic regios are exposed to the aqueous environment on either side of the membrane - Peripheral proteins are attached to the bilayer by lipid groups (dolichol)

10. Human red cells in scanning elektron microscope

11. Membrane skeleton network of proteins under the plasma membrane. In red cells the membrane skeleton is formed by spectrin, actin filaments and attachment proteins

12. Glycocalyx: a coat of poly- a oligosaccharides on the surface of plasma membrane

13. Extracelullar matrix (ECM): Complex network of polysaccharides and proteins produced by cells of connective tissue (fibroblasts, chondrocytes, osteocytes etc.) Main components: collagens, elastin – structural proteins fibronectins – fibrous adhesive proteins interconnecting ECM to a and laminin s meshwork proteoglycans – gly c oproteins forming a gel ECM calcified in bone and teeth Ropelike in tendon Transparent in cornea Plant cell wall – specific type of extracellular matrix

14. Cellular interactions and cell adhesion carry out a structural role, important in cell migration, growth, immunological function, cell recognition, tissue repair, differentiation and embryogenesis

15. Cell-to-cell interaction: C ell adhesion molecules ( CAM ): cadherin, Ig superfamily CAM, mucin-like CAM, integrins selectins

16. Basal lamina T hin tough sheet of extracellular matrix . Composition : collagen t y pe IV tensile strength laminin provides adhesive sites for integri n molecules in the plasma membrane of epithelial cells other proteins

17. Structure and function of basal lamina

18. Keratinocyte crawling over surface

19. Model of focal adhesion Components: ECM Integrin Vinculin Talin Actin filaments

20. Plasmamembr ane a nd cell migration Cell crawling – formation of filopodia (thin stiff protrusions) and lamelipodia (thin sheet-like extensions) – due to actin polymerization. The new position of the plasma membrane is fixed by focal adhesion complexes Contraction of a part of the cytoplasm, invagination of the plasma membrane or invagination of cell layers due to the activity of actin-myosin I or actin-myosin II complexes: actin filaments are anchored to the plasma membrane. Actin filaments slide over each other, the sliding is mediated by myosin motors.

21. Key terms 1. Biomembranes – overview of the structure and functions 2. Development of membrane concept: lipid layer, lipid bilayer, phospholid bilayer, localization of membrane proteins 3. Structure of the phospholipid bilayer 4. Hydrophilic head and hydrophobic tails. Self-assembly of the bilayer. Lipid asymmetry. Membrane rafts. Liposomes. 5. Model of the fluid mosaic. I ntegr al a peripheral proteins. 6. Hydrophobic regions of integral proteins 7. Membrane glycoproteins 8. Glycocalyx 9. Extracelular matrix: main components: collagen, elastin, fibronectin, laminin, proteoglycans

22. Key terms – cont. 10. Basal lamina: components and function 12. Plasmamembrane and cell migration: cell crawling and contractile movements 13. Focal adhesion