CHAPTER 7 Interactions Between Cells and Their Environment

Introduction • Cells interact with extracellular material to form defined tissues. • These interactions are crucial to the formation of epithelial tissue and connective tissue, which are crucial for various cellular activities.

Overview of cell organization into tissues

7. 1 The Extracellular Space (1) • The glycocalyx (cell coat) is formed from carbohydrate projections form the plasma membrane. • Glycocalyx mediates cell-cell and cellsubstratum interactions.

The Extracellular Space (2) • The extracellular matrix (ECM) is an organized network beyond the plasma membrane. – It often plays a regulatory role in determining shape and activities of the cell.

The Extracellular Space (3) • ECM (continued) – The basement membrane (basal lamina) is a continuous sheet that underlies epithelial tissue and surrounds blood vessels. • Helps maintain cells attached. • Serves as substratum for cell migration. • Forms a barrier to macromolecules.

The basement membrane

Organization of the ECM

The Extracellular Space (4) • Collagens – fibrous glycoproteins found only in the ECM. – Collagen is the most abundant protein in the human body. – Provide high tensile strength. – Each collage is restricted to particular locations in the body. – All collagens are a trimer of polypeptide chains wound around each other.

The structure of collagen I

The Extracellular Space (5) • Collagens (continued) – Provide the insoluble framework that determines mechanical properties of the matrix. – Abnormalities in collagen formation lead to serious disorders.

The Extracellular Space (6) • Not all collagens form fibrils. • Collagen type IV is non-fibrillar, and is restricted to the basement membrane.

The Extracellular Space (7) • Proteoglycans – protein-polysaccharide complex, with a the core protein attached to glycosaminoglycans (GAGs). – Have a repeating disaccharide structure. – Negatively charged GAGs attract lots of cations, which in turn attract water forming a porous, hydrated gel.

Structure of a proteoglycna complex

The Extracellular Space (8) • Fibronectin (Fn) – a linear array of distinct polypeptides giving it a modular structure. – Each polypeptide is about 30 Fn modules. – Fn modules are found in other proteins too. – Fn has binding sites for other components of the ECM. – Fn guides migrating cells during embryogenesis.

Structure of fibronectin

Cell migration during embryogenesis

The Extracellular Space (9) • Laminins – extracellular glycoproteins consisting of three polypeptide chains linked by disulfide bonds. – Help cell migration during development. – Components of basement membranes.

The Extracellular Space (10) • Dynamic Properties – The ECM can be stretched during tension. – ECM materials degraded by matrix metalloproteinases (MMPs). – MMPs possibly involved in tissue remodeling, embryonic cell migration, wound healing , and formation of blood vessels.

7. 2 Interactions of Cells with Extracellular Materials (1) • Integrins – family of membrane proteins composed of heterodimers with α and ß subunits. – Have a major role in integrating extracellular and intracellular environments. – Another role is adhesion of cells to their substratum or other cells.

Model of integrin activation

Interactions of Cells with Extracellular Materials (2) • Integrins (continued) – Linkage between integrins and their ligands mediates adhesion between cells and their environment. – Binding of proteins to integrins is facilitated by tripeptide RGD.

Interactions of Cells with Extracellular Materials (3)

Interactions of Cells with Extracellular Materials (4) • Integrins (continued) – Cytoplasmic domains of integrins contain binding sites for a variety of cytoplasmic proteins. – Integrins make the connection between the ECM and the cytoskeleton.

Interactions of Cells with Extracellular Materials (5) • Focal adhesions – scattered, discrete sites for cell adhesion to their substratum in vitro. – They may act as a type of sensory structure. – Are also implicated in cell locomotion.

Focal adhesions

Forces exerted by focal adhesions

Interactions of Cells with Extracellular Materials (6) • Hemidesmosomes – basal attachments of epithelial cells to the basement membrane in vivo. – Contain a dense plaque with filaments consisting of keratin. – Keratin filaments are linked to the ECM by membrane-spanning integrins.

Hemidesmosomes

7. 3 Interaction of Cells with Other Cells (1) • Cells have surfacerecognition sites that maintain organization

Interaction of Cells with Other Cells (2) • Selectins – family of integral membrane glycoproteins that bind to sugars on the surface of cells.

Interaction of Cells with Other Cells (3) • Selectins (continued) – Contain a small cytoplasmic domain, a single membrane-spanning domain, and a large extracellular segment. – Three types: • E-selectin – on endothelial cells. • P-selectin – on platelets and endothelial cells. • L-selectin – on white blood cells.

Interaction of Cells with Other Cells (4) • Immunoglobulin superfamily (Ig. SF) – most proteins are involved in immune functions. – Most Ig. SF molecules mediate interaction of lymphocytes with cells required or immune response.