On the Mechanobiology of Collagen Growth and Remodelling
General Material Designation
[Thesis]
First Statement of Responsibility
Siadat, Seyed Mohammad
Subsequent Statement of Responsibility
Ruberti, Jeffrey W.
.PUBLICATION, DISTRIBUTION, ETC
Name of Publisher, Distributor, etc.
Northeastern University
Date of Publication, Distribution, etc.
2020
GENERAL NOTES
Text of Note
236 p.
DISSERTATION (THESIS) NOTE
Dissertation or thesis details and type of degree
Ph.D.
Body granting the degree
Northeastern University
Text preceding or following the note
2020
SUMMARY OR ABSTRACT
Text of Note
How organized collagenous structure can arise and grow from a cluster of cells remains one of the most important basic science questions associated with connective tissue research. Despite more than a century of research, there are currently no widely accepted mechanistic models of formation, growth, and remodeling of collagen fibrils. It has been hypothesized in our research group that collagen monomers and enzymes are in a dynamic equilibrium with existing fibrils. Tensile forces on fibrils can shift this equilibrium and change the balance between molecular association and dissociation. Here, we sought to answer this question: Does fibril strain promote the molecular assembly of collagen? To investigate this question, individual collagen fibrils were stretched to 0%, 4%, and 6% strain between two microneedles and exposed to a subthreshold concentration of fluorescently labeled collagen molecules to quantify molecular association onto the stretched fibrils. It was shown that labeled monomers rapidly incorporate onto all tested fibrils and reach a plateau. The time to reach plateau was significantly faster for the stretched fibrils (15.6, 7.0, and 6.0 minutes for fibrils under 0%, 4%, and 6% strain, respectively). Analysis of the fibril intensity and photobleaching data indicated that the association rate was significantly higher for fibrils under 6% strain compared to fibrils under 0% and 4% strain, increasing the association rate by 100%. It was concluded that mechanical stresses and strains could increase fibril growth by decreasing the activation energy required for reaction between monomers and fibrils and also by setting fibrils in a lower state of energy, increasing the association rate of monomers and fibrils.