Helical model of nucleation and propagation to account for the growth of type I collagen fibrils from symmetrical pointed tips: a special example of self-assembly of rod-like monomers.

Abstract

A model was developed to account for the recent observations indicating that type I collagen fibrils assembled in vivo grow from symmetrical pointed tips. The essential features of the model are (i) a distnctive structural nucleus forms at each end of a growing fibril and growth of the fibril then proceeds by propagation ofthe two structural nuclei, METHODSComputer simulations of fibril models were carried out with a Silicon Graphics workstation. Each collagen monomer was represented as a cylinder with a length defined as 4.4 D periods. Models for fibril assembly were simulated by addition of one monomer at a time according to rules for binding through unidirectional 3.4 D-period overlaps or 0.4 D-period overlaps as described in Results. Interactive programs were written so that the models could be rotated in three dimensions after each monomer addition and so that different growth patterns could be explored in two or three dimensions. RESULTSCriteria for the Model. The major criteria for developing a model were that it account for the following observations made on fibrils assembled de novo at 370C (Fig. 1): (i) in cross-section, the a-tips were circular down to a tip of <25 nm (22,24); (ii) axially, the a-tips were near-paraboloidal, as indicated by a decrease in mass toward the tip that was an average of 17 molecular D segments per D period and that was linear over 100 or more D periods (24); (iii) the a-tips on both short and long fibrils were essentially the same (24), an observation implying that the contour remained constant as the fibrils grew; (iv) the (-tips were also near-paraboloidal but were more irregular with slopes that varied from 50 to 200 molecular D segments per D period (24); (v) after the (3-tips appeared, both a-tips and (-tips grew simultaneously on the same fibril (24); (vi) all monomers were oriented so that the N termini were directed toward the tips (22, 24); and (vii) the shafts of all the fibrils formed under the same conditions had about the same diameters (21, 23).Initial Considerations of Alternative Models. Initial considerations indicated that the observations could not be explained in any simple manner by several previous suggestions about fibril growth (Table 1). For example, assembly driven primarily by surface tension and liquid-like forces (see ref.11) cannot readily explain the persistent differences in con§To whom reprint requests should be addressed. 9860The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.

Macromolecular Specificity of Collagen Fibrillogenesis

“…Therefore, we concluded that in vitro fibrillogenesis of collagen I was not subject to a stringent lateral growth control. Instead, fibrils were formed by stochastical nucleation followed by propagation accretion of single collagen molecules, consistently with the model proposed by Silver et al (42).…”

Inhibition of the Self-assembly of Collagen I into Fibrils with Synthetic Peptides

“…A third possibility is that binding through the N-telopeptides does not play an important role in fibril assembly until a core of a microfibril is formed, and it is only important for lateral growth of the fibril. The last suggestion is consistent with one of the proposed helical models for growth of microfibrils from paraboloidal tips (25). The model required one specific binding step governed by one rate constant (k 1 ) for assembly of monomers in a 1D-stagger to form a Smith-type microfibrillar core and to regulate longitudinal growth of the fibril.…”

“…One model (25) was based on the assumption that the initial core of the fibril was a pentameric microfibril and that the fibril grew by the addition of monomers in a helical pattern. Simulations of the model suggested that as little as two specific binding steps were required, first for assembly of the microfibrillar core and then a structural nucleus with about the same diameter as the final fibril.…”

Collagens—structure, function, and biosynthesis

“…The ability for the ''self-assembly'' is encoded in the structure of the collagens and several models describe the mechanism for the periodic fibrillar assembly. Hydrophobic and electrostatic interactions of collagen monomers are involved in the quarter-staggered arrangement of collagen monomers, which may aggregate into five-stranded fibrils and subsequently into larger fibrils [3,99,100] (Fig. 2).…”