Collagen self-assembly
Subtitle: a complementary experimental and theoretical perspective
By: by Darren Anderson.
Published: 2006
Language: eng
Number of pages: 349
ISBN-13: 9780494157466
Description: Collagen is the major structural protein in mammals, and forms the basis of a variety of tissues essential for animal life, including bone, skin, teeth, cornea, tendon, and others. It self-assembles---both in vivo and in vitro---into a variety of biologically important structures, and this self-assembly process is highly dependent on solution pH, ionic strength, and the concentration of the collagen monomer. Kinetic studies demonstrating these dependencies are presented for the formation of the most important aggregate, native type collagen. The cold dissociation of collagen that does not contain complete non-helical telopeptide regions is also demonstrated. Based on these studies, five different types of collagen intermediates are identified and a partially hierarchical fibrillogenesis mechanism is proposed, along with a detailed kinetic model. In order to further understand collagen fibrillogenesis at a molecular level, a previously predicted structure of the collagen monomer is completely relaxed using condensed phase molecular dynamics simulations. For validation purposes, several experimentally solved model collagen structures are simulated in the same way, and the simulation results agree with the crystal structures to within the experimental error. Therefore, a structure of the collagen monomer is proposed that comprises the most complete model currently developed. This model forms the basis for two sets of simulations aimed at explaining the formation of several of the polymorphisms of collagen. First, a three-dimensional analysis of the interactions between collagen monomers in fibrillar aggregates is presented, including hydrophobic-hydrophobic and electrostatic interactions. An examination of these interactions as a function of overlap between monomers demonstrates the origin of the topological regularity in native type collagen. Second, a detailed molecular model for formation of segmental long spacing crystallites of collagen is presented, involving bridging of in-register collagen monomers by nucleotide triphosphate moieties at colocalized acidic and basic residues. The proposed model is confirmed using molecular mechanics and dynamics simulations.
Notes: Source: Dissertation Abstracts International, Volume: 67-06, Section: B, page: 3149.

Thesis (Ph.D.)--University of Toronto, 2006.

Includes bibliographic references.

Electronic version licensed for access by U. of T. users.