Molecular Cell Biology

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 pH 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 Irregular CT

Dense Regular 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 23-47a 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 31-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

Dont 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