Lecture 3 – TUL 1

Types of Mechanical Loads

the body experiences various mechanical forces daily:

  • tension: pulling or stretching forces

  • compression: pushing or crushing forces

  • shear: forces that cause layers to slide past each other

  • torsion: twisting forces

  • bending: combination of tension and compression


tissues adapt their structure and function based on the loads they experience


Collagen: The Major Tensile Molecule

  • 42 genes in the human genome encode distinct collagen chains

  • all collagens share a common property: they’re formed from a triple helix of alpha-chains

  • the repeating amino acid sequence is Gly-X-Y

    • X is often proline

    • Y is often hydroxyproline


Collagen Synthesis

  1. Synthesis of pro-alpha chain:

contains Gly-X-Y repeats; synthesised in the rough ER

  1. Self-assembly of three pro-alpha chains:

three chains wrap around each other

  1. Pro-collagen triple helix formation:

formation of pro-collagen molecule with pro-peptide ends; secreted into ECM

  1. Cleavage of pro-peptide:

pro-peptides are removed by proteases outside of the cell

  1. Self-assembly into fibril:

collagen molecules assemble into fibrils (visible banding pattern on EM)

  1. Aggregation into fibre:

fibrils bundle together to form larger collagen fibres


vitamin C is essential for lysyl hydroxylase, the enzyme that hydroxylates proline and lysine, enabling proper coiling


Collagen-Related Diseases

Scurvy (Vitamin C Deficiency)

  • Lack of vitamin C → impaired hydroxylation of proline and lysin → unstable collagen triple helix

  • Rotten teeth, bleeding gums, bleeding from mucous membranes, bowed legs

  • Areas with high collagen turnover is affected most


Osteogenesis Imperfecta

  • Genetic mutation in genes encoding collagen type I

  • pathology: insufficient and poor-quality collagen (improper coiling)

  • brittle bones, bone deformities, weak tendons, abnormal teeth/skin, hearing loss, blue sclerae

  • ranges from mild to severe/debilitating

    • debilitating: (of a disease or condition) making someone very weak and infirm


Stickler Syndrome

  • Genetic mutation in COL2A1 gene → defective collagen type II

  • flattened facial appearance (underdeveloped bones), nearsightedness, hearing loss, early-onset osteoarthritis and joint pain


Proteoglycans: The Soluble Polymers

a proteoglycan consists of a core protein + one or more covalently attached glycosaminoglycan (GAG) chains

GAG Characteristics

  • long, linear carbohydrate polymers

  • negatively charged due to sulphate and uronic acid groups

  • consists of repeating disaccharide units

  • function: fill space, act as hydrated gels, resist compression


Hyaluronan (Hyaluronic Acid)

  • the only GAG that’s not sulphated

  • ubiquitously expressed in the body

  • binds large amounts of water → important for tissue hydration, joint lubrication, and molecular diffusion


Aggrecan: Key Load-Bearing Proteoglycan

  • major proteoglycan of cartilage

  • rich in chondroitin sulphate and keratan sulphate GAGs

  • forms large aggregates by binding to hyaluronan (HA) via link protein

  • highly negatively charged → attracts water → forms a stiff gel

  • provides resistance to compressive loads in cartilage and intervertebral discs

  • loss of aggrecan occurs in osteoarthritis


ECM Turnover and Remodelling

  • cells produce and degrade ECM via proteases

  • collagenases: break down fibrillar collagen

  • ADAMTS: break down proteoglycans

  • ECM degradation and replacement occurs throughout life; dysregulation leads to disease