1. Barrier Function &
Biomechanical Properties of
the Skin
Maha Adel Shaheen, MD
Professor of Dermatology & Venereology
Ain Shams University

2. Skin Structure
1- Epidermis
- Stratum Corneum
- Viable Epidermis
← BMZ →
2- Dermis
3- Hypodermis
(Subcutaneous fat)

6. Viable Epidermis
• Basal Layer
stratum germinativum
• Spinous Layer
intercellular bridges
(desmosomes)
• Granular Layer
(KHG – Odland bodies)

9. Stratum Corneum
• 15-20 layers of terminally
differentiated keratinocytes.
• Dead non-nucleated thin
flat cells (squames)
(corneocytes).
• Held together by lipids and
desmosomes.
• Function: Epidermal Barrier

10. Epidermal Barrier
(Brick and Mortar Wall)
• Site: lower stratum
corneum.
• Function: protection
from water loss &
noxious physical,
mechanical & chemical
insults.
• Structure:
1- Corneocytes (hard
building blocks).
2- Intercorneocyte lipids
(space filling mortar).

11. Corneocytes
1- KIF cytoskeleton
Tightly bundled keratin
intermediate filaments
aligned ≈ to the skin
. surface
2- Cornified cell envelope
(CE)
• Uniform band located
beneath the KC
plasma membrane.
• Formed of cross linked
specific structural proteins.

12. Keratin Intermediate Filaments
- Rope-like fibers extending
from nucleus periphery.
- Mechanical support.
- Tissue specific expression
of heterodimers
(K5/K14 - K1/K10)

13. Structure of Intermediate
Filaments
• Two dimers of cytokeratin group
into a keratin tetramer by anti-parallel
binding.
• This cytokeratin tetramer is
considered to be the main building
block of the cytokeratin chain.
• By head-to-tail linking of the
cytokeratin tetramers, the
protofilaments are originated,
which in turn intertwine in pairs to
form protofibrils.
• Four protofibrils give place to one
cytokeratin filament.

14. Organization of KIF (Bundling) in
Epidermal KC

15. Desmosomes
(Desmosome - Tonofilament Complexes)

17. CE Proteins
• Involucrin
• Loricrin
• Keratolinin
• pro (Filaggrin)
• Desmosomal proteins:
- desmoplakin
- envoplakin
- .............

19. Inter-corneocyte Lipids (mortar)

20. • Keratinization specific
multilamellar lipid
sheets in-between
corneocytes
• Formed in the granular
cell layer Odland
(lamellar) bodies
- Ceramides
- Cholesterol & esters
- Free fatty acids
- phospholipids

21. Defects of Skin Barrier
(Broken Bricks - Weak Mortar)
1- Atopic Dermatitis
2- Psoriasis
3- Lamellar Ichthyosis
4- Netherton Syndrome
5- Contact Dermatitis

22. Basement Membrane Zone
( BMZ )
• Histopathological BMZ
(PAS +ve)
• Ultrastructural BMZ
• Molecular BMZ

23. Basement Membrane Zone

24. Skin BMZ

25. BMZ - Hemidesmosome

26. Human skin basement membrane as
a target of autoimmune diseases
Diseases chch by autoantibodies
directed against hemidesmosome
1- Bullous pemphigoid
2- Linear IgA bullous dermatosis
Diseases chch by autoantibodies
directed against lower lamina lucida
1- Cicatricial pemphigoid with
autoantibodies to bullous
pemphigoid antigen
2- Anti-laminin cicatricial pemphigoid
3- Anti-p105 pemphigoid
Diseases chch by autoantibodies
directed against sub-lamina densa
1- Epidermolysis bullosa acquisita
2- Bullous SLE

27. Molecular Basis of Inherited Skin
Diseases
• Epidermolysis bullosa (EB)
EB Simplex ----- K5 & K14
EB Junctional ----- Laminin
EB Dystrophic ----- Collagen VII
• Ichthyoses
Ichthyosis Vulgaris ---- Profilaggrin
XLRI ------- Steroid sulfatase
BIE ------ K1 & K10
• Palmoplantar Keratodermas
• Ectodermal Dysplasias

28. Sites of Skin Cleavage in Different
EB Syndromes

30. Extracellular Matrix
• Any material produced by cells &
secreted into the surrounding medium.
• ECM is produced by cells & influences
the behavior of cells.
3 major components
1- Fibrous elements (collagen, elastin,
reticulin)
2- Link proteins (fibronectin, laminins,…)
3- Space-filling molecules ( GAGs)

31. Extracellular Matrix

32. Extracellular Matrix
Fibrillar Matrix (structural proteins)
• Collagen - Elastin - Reticulin
Extrafibrillar Matrix
• Glycosaminoglycans (GAGs)
• Proteoglycans
• Hyaluronic acid
Glycoproteins (adhesive function)
• Laminins, fibronectin, vitronectin .…..

33. ECM Function
A- Structural Function:
• Skin elasticity, resilience, tautness.
• Strong adherence between epidermis
and dermis by BMZ anchoring
complexes -------> resistance against
external sheering forces.
B- Regulation of cellular functions:
• Cell adhesion, migration, division,
signaling, apoptosis …..

34. Collagen

35. Collagen Triple Helix

36. Collagen Molecule
• A triple helix of three extended protein
chains wrapped around one another.
• Numerous rod like collagen molecules
cross-link together to form un -
extendable collagen fibrils.
• Collagen fibrils are striped because of
the regular repeating arrangement of
the collagen molecules within the fibril.

37. Collagen Basic Structure

40. Procollagen Molecule

41. Collagens
(26 types – 44 genes)
Skin Collagens
• Collagen I, II, III
• Collagen IV (BM collagen)
• Collagen VII (Anchoring fibrils)

43. Elastin molecule uncoils when the fiber is stretched and
spontaneously recoils when the stretching force is relaxed

44. Extrafibrillar Matrix
• Glycosaminoglycans (GAGs)
Large polysaccharide chains made up
of repeating disaccharide units that are
negatively charged and hold a large
amount of water compared to other
ECM molecules
• Proteoglycans
Protein and polysaccharide complexes

45. Extrafibrillar Matrix

47. Mechanical Skin Properties
Tension: taut - tense - stretched firmly -
not slack - resists deforming forces.
Elasticity: recoils or springs back to its
original length or shape after being
stretched or squeezed.
Resilience: springy- adaptive - readily
recovering from shock.
Tensile Strength: the degree to which it
can be elongated before it tears.

48. Mechanical Skin Properties
Cytoskeleton
Supports the cell and gives it its shape
Glycosaminoglycans( GAGs) & Proteoglycans
Viscoelastic properties & resistance to compression
Collagen fibers
Tensile strength (resistance to breaking or tearing)
Elastic fibers
Tension, resilience, elasticity

49. Abnormalities of Dermal
Fibrous & Elastic Tissue

50. Ehlers-Danlos Syndrome (EDS)
Skin Hyperelasticity

51. EDS Joint Hypermobility
1. More than 10º hyperextension of
the elbows.
2. Passively touch the forearm
with the thumb, while flexing
the wrist.
3. Passive extension of the fingers
or a 90º or more extension of
the fifth finger (Gorling’s sign).
This is used as a “Screen Test”.
4. Knees hyperextension greater
than or equal to 10º.
5. Touching the floor with the
palms of the hands when
reaching down without bending
the knees. This is possible as
a result of the hypermobility of
the hips, and not of the spine as
it is commonly believed.

52. EDS Joint Hypermobility

53. Cutis Laxa
Hyperextensible non elastic skin

54. Pseudoxanthoma Elasticum (PXE)

55. PXE
Calcium salts deposited on abnormal elastic fibers

56. Solar or Senile Elastosis
Favre-Racouchot Syndrome

58. Abnormalities of Dermal
Extrafibrillar Matrix

59. Cutaneous Mucinoses
A heterogeneous group of conditions
caused by dermal fibroblasts
producing abnormally large amounts of
glycosaminoglycans → focal or diffuse
dermal deposition.

60. H&E: bluish, ffeeaatthheerryy mmaatteerriiaall
bbeettwweeeenn ccoollllaaggeenn bbuunnddlleess

61. Mucin Stains
• Colloidal Iron
• Alcian Blue
• Toluidine Blue
• Incubation of tissue in
hyaluronidase eliminates the
staining, confirming the presence
of mucin

62. Lichen myxedematosus - Papular
mucinosis - Scleromyxedema
The etiology is unknown. The
disease is commonly associated
with plasma cell dyscrasia.
The basic defect ≈ a fibroblast
disorder → increased mucin
deposition in the skin.
Most patients have a
monoclonal paraprotein band,
usually IgG type.
The association between this
paraprotein and the mucin
deposition is not clear, and the
protein does not directly
stimulate fibroblast
proliferation.

63. Why Shar Pei Dogs Have So
Many Wrinkles
• The genetic alteration in this
breed multiplies the activity
of an enzyme responsible
for an excessive production
of hyaluronic acid which
gathers under the skin and
produces wrinkles.
• Understanding this
molecular mechanism will
be used to learn more about
human disorders such as
mucinosis and to gain more
knowledge on the ageing
process.

64. Mucopolysaccharidoses
• A group of metabolic disorders caused by the absence or
malfunctioning of lysosomal enzymes needed to break down
glycosaminoglycans.
• Patients either do not produce enough of one of the 11
enzymes required to break down these sugar chains into
simpler molecules, or they produce enzymes that do not work
properly.
• Over time, these GAGs collect in the cells, blood and
connective tissues.
• The result is permanent, progressive cellular damage which
affects appearance, physical abilities, organ and system
functioning, and, in most cases, mental development.

65. Lipoid Proteinosis
• Skin scarring, beaded eyelid papules, laryngeal
infiltration → hoarseness, Infiltrates in the tongue
and its frenulum limit lingual movements and cause
speech difficulties.
• PAS positive hyaline material in the skin, upper
aerodigestive tract & internal organs.
• Mutations in the extracellular matrix protein 1 gene
(q21) .
• ECM1 = glycoprotein that binds to perlecan, the
major heparan sulphate proteoglycan of the BM, as
well as to fibrillar proteins (“biological glue” in the
dermis, helping to regulate basement membrane and
interstitial collagen fibril macro-assembly ).