Multimodal Failure Mechanics in the Collagen Fibril

Collagen's evolutionary longevity is a tribute to the survival value of its complex, self--assembled structure. While both elasticity and overload damage have been studied extensively at the light microscope level in connective tissues, it is below that scalereally at the nanometer scalewhere mechanical load is borne. It is there that collagen's strength is achievedand perhaps more important for survival, where its toughness is determined. For the last 10 years or so, I have been interested in two fundamental questions:

(i) What does mechanical damage in collagen look like at its most fundamental levels?

(ii) Are there structural motifs for damage in collagen that activate physiologically appropriate cellular repair or replacement? These are questions of deep import for understanding the biomechanical evolution of the collagen fibril and for rational design of processed collagen products which can mimic native toughness and modulate inflammation and healing.

We recently demonstrated that overloading of tendon collagen produces a characteristic, local, nano-scaled “kinking” of collagen fibrils (5200 nm dia.). Fibril-level damage leads to thermodynamic instability of the packed collagen molecules, consistent with local denaturation. Enzymolysis and very high magnification SEM (50-70kX) of overloaded tendons have shown that a sub-set (only) of the sub-fibrils at the kink zones are disrupted while others remain. Repeated plastic overload without rupture produces a linear densification of the kinks along individual damaged fibrils. The collagen fibril has thus been revealed to be unexpectedly heterogeneous: both across its diameter and along its length. We have a working theory that the local “kink” failure mechanism has 2--way evolutionary value: toughening tissues like tendons to prevent catastrophic failure while providing the structural cues that guide resorption and/or repair of damaged fibrils. I believe this knowledge can be used.

I propose to further explore the fundamental structuro--mechanical questions which have emerged from our work to date, applying SEM, cryo-TEM, and AFM plus finer-scale, stretch-retained samples to reduce heterogeneity of damage, thereby visualizing kink zone failures before elastic rebound. We will also produce laboratory-extruded collagen fibres to study the extent to which the heterogeneous fibril assembly necessary to the discrete plasticity mechanism is innate to collagen, and what interventions must be applied to produce it for technological value. Finally, we will study the question of whether the serial kink zones which form in damaged fibrils are periodic in nature or stochastically determined. With that knowledge, we will explore fibril-to-fibril propagation of kink formation and seek to produce a model which can couple nanoscale molecular/fibril damage to micron-scale fibre failure.