BIO 121 Molecular Cell Biology Lecture Section IV

BIO 121 – Molecular Cell Biology Lecture Section IV A. Cells in the Context of Tissue, Organ and Organismal Architecture B. Wound Healing

Four Types of Vertebrate Tissue 1. Epithelium 2. Connective Tissue 3. Muscle 4. Nervous Tissue

1. Architecture of Epithelium • Simple, Stratified, Pseudostratified, Transitional • Squamous, Cuboidal, Columnar • Ciliated or not • Examples: – – Small Intestine = Simple Columnar Epithelium Trachea = Ciliated Pseudostratified Columnar Epithelium Blood Vessel = Simple Squamous Epithelium Skin = Stratified Squamous Epithelium

Structure equals Function – Small Intestine: Simple Columnar Epithelium = absorption – Trachea: Ciliated Pseudostratified Columnar Epithelium = filtering debris – Blood Vessel: Simple Squamous Epithelium = gas exchange – Skin: Stratified Squamous Epithelium = protective physical barrier

Simple, Columnar Epithelium Function: 1. absorption of nutrients 2. enzymatic digestion at neutral p. H 3. multiple defensive mechanisms

4 Cell types in Small Intestine

Small Intestine

Cellular Adhesion in Small Intestine Desmosomes Hemidesmosomes Adherens Junctions Occluding Junctions

Tracheal Epithelium Ciliated Pseudostratified Columnar Epithelium with Goblet Cells 1. Mucus traps dust and airborne microorganisms 2. Ciliar waving gets rid of unwanted material

The Vasculature: Simple, Squamous Epithelium Gas Exchange Fluid Exchenge

Epidermis of Skin Stratified Squamous Epithelium Creates tough, waterproof barrier

Differentiation and Direction of Movement in Epidermis Cornification is the overproduction of cytokeratins, ECM and the adhesions to a degree that stops cellular metabolism.

2. Mesenchymal Cell Types and Connective Tissues

Figure 23 -52 Molecular Biology of the Cell (© Garland Science 2008)

The Fibroblast

Loose Connective Tissue Dense Regular CT Dense Irregular CT Elastic Connective Tissue

The dermis is as complex as the epidermis and contributes greatly to skin function

Cartilage and the Chondrocyte

Lacunar Structure of the Hyaline Cartilage Extremely low blood flow

Osteoblasts Lacunar structure of the long bones

Cortical Bone vs. Spongy Bone

Cell Types of the Bone Marrow of Long Bones has Stem Cells

Start out as cartilage models built by chondrocytes Chondrocytes hypertrophy, calcify and die Osteoblasts and osteoclasts finish up

The Adipocyte Mesenchymal Stem Cells are a continuous source of adipocytes

3. Contractile Tissue Figure 23 -47 a Molecular Biology of the Cell (© Garland Science 2008)

Arteries, veins Lymphatic vessels Gastrointestinal tract Respiratory tract Urinary bladder Reproductive tract Urinary tract Iris of the eye Erector pili of skin

4. Nervous Tissue

Nerve Bundles

Cutaneous Wound Healing The skin is a complex organ. . .

Many cells and activities involved

Many cells and activities involved in Healing Clotting Scarring Re-establishing Function

• Four overlapping stages to wound healing – Hemostasis – Inflammation – Proliferation – Maturation

Blood flows into the exposed ECM of the injured tissue.

RBC and Platelets Trapped in Fibrin Clot

Clotting factor VII from the blood contacts tissue factor on cells in the damaged tissues to activate clotting

Platelet activation in the. clot makes them sticky and releases their signal storage vesicles © 2000 by Lippincott Williams & Wilkins Camacho A , Dimsdale J E Psychosom Med 2000; 62: 326 -336

Positive feedback activates even more

Platelet activation releases growth factors by regulated secretion

Inflammation is a process mediated primarily by WBC as part of our innate immunity - Resident mast cells and macrophages - Recruited monocytes and neutrophils

Resident mast cells also degranulate rubor = redness calor = heat tumor = swelling dolor = pain

Activated mast cell activities

Figure 1 Development and differentiation of macrophages. Rickard A J , Young M J J Mol Endocrinol 2009; 42: 449 -459 © 2011 Society for Endocrinology

Activated macrophage activities

Neutrophil Diapedesis

Activated neutrophils are phagocytic

Proliferation re-establishes tissue function • Reconnection of the dermal connective tissue • Integrity of the epidermal layers • Re-establishment of blood flow

Reconnection of the dermal CT

Cell Migration or “Crawling” • The Basic Mechanism – Triggered by signals from outside the cell – Actin-myosin based movement – Requires attachments to outside to pull against – Gotta’ drag all of the cell contents along for the ride

Chemotaxis Circumferential receptors Rho-family GTPases (monomeric) Rho-dependent kinases 1. Actin monomer nucleotide exchange 2. Actin fiber polymerization and disassembly 3. Myosin motor ATPase activity

Figure 17 -62 (part 1 of 3) Molecular Biology of the Cell (© Garland Science 2008)

Formation of the scar matrix 1. 2. 3. 4. glycosaminoglycans proteoglycans fibrous proteins elastic proteins

Re-establishment of the epidermal epithelium involves both mitosis and epithelial migration

Also must reform the basal lamina

Re-epithelialization below the scab scar Fi

Model depicting α 3β 1 -integrin-mediated functions of epidermis that contribute to wound healing. Mitchell K et al. J Cell Sci 2009; 122: 1778 -1787 © 2009 by The Company of Biologists Ltd

Figure 23 -34 Molecular Biology of the Cell (© Garland Science 2008)

Maturation Phase

Wound contraction by myofibroblasts

Stitches Perform Wound Contracture

Collagen Remodeling

A scar never reaches the strength of undamaged tissue

Healing Abnormalities • Failure to heal: Excessive Inflammation • Excessive scarring: Wound Fibrosis – Hypertrophic Scarring – Keloid Scarring

Biofilms May Block Healing

Hypertrophic scars result from failed fibroblast contracture Don’t extend beyond the original wound edge

Keloid scars result from excessive TGF-b receptors on fibroblasts Extend to fibroblasts outside the wound

People have exploited these conditions to create the ‘keloid tattoo’