# CONTROL OF COLLAGEN METABOLISM AND CROSSLINKING

> **NIH NIH R01** · UNIVERSITY OF SOUTHERN CALIFORNIA · 1988 · $193,531

## Abstract

The distribution, deposition and stabilization of different collagen types
are crucial for the formation and maintenance of functional connective
tissue matrices.  We plan to investigate the extent and importance of
aldehyde-derived and disulfide-derived crosslinks between the same and
different collagen types during tissue development and maturation.  We will
use both in vitro and in vivo models of fibrillogenesis to study the
location and temporal sequence of crosslink formation.  These data will
identify collagen packing arrangements in fibrillar and non-fibrillar
extracellular matrices.

Collagen fibers will be reconstitiuted from type I and/or type III collagen
using mixtures of labeled lathyritic and unlabeled normal collagen.  This
will permit the identification of amino and aldehyde donors in crosslink
formation.  The frequency and location of crosslinks along different kinds
of collagen chains will be determined by collagenase digestion and 2-D CNBr
mapping.  The diversity of crosslink patterns between homopolymers and
heteropolymers in skin, bone, tendon and gramulation tissues will be
explored using methods to identify and purify crosslinked peptides
containing the carboxy-terminal CNBr peptides of type I and type III
collagen.  This will be accomplished by using monoclonal antibodies to
a1(I)-CB6 and a2(I)-CB5, and a sulfhydryl affinity column for a1(III)-CB9.
These peptides will be further fractionated by 2-D CNB4r mapping and then
characterized by tryptic fingerprinting and amino acid analysis.

The presence and formation of intermolecular disulfide crosslinks in type
III collagen has been demonstrated in our laboratory.  We will test whether
these crosslinks allow type III collagen to form a transient early
scaffolding for developing tisuses by identifying type III disulfide bonded
polymers during formation of granulation tissue.  Polymers will be
identified by sedimentation and 2-D mapping.

Finally, the structure of EC collagen will be investigated with emphasis on
the sequence and polarity of the peptides.  The molecular interactions of
EC collagen in basement membrane architecture will be analyzed by
determining the location of crosslinked CNBr peptides beteen itself and
type IV collagen.  Crosslinked peptides in Descemet's membrane an basement
membrane derived from cultured corneal endothelial cells will be labelled,
fractioned by 2-D mapping and characterized by tryptic fingerprinting on
HPLC.

## Key facts

- **NIH application ID:** 3154685
- **Project number:** 5R01AR010358-21
- **Recipient organization:** UNIVERSITY OF SOUTHERN CALIFORNIA
- **SAM.gov UEI:** G88KLJR3KYT5
- **Principal Investigator:** MARCEL E NIMNI
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1988
- **Award amount:** $193,531
- **Award type:** 5
- **Project period:** 1979-07-01 → 1991-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3154685

## Citation

> US National Institutes of Health, RePORTER application 3154685, CONTROL OF COLLAGEN METABOLISM AND CROSSLINKING (5R01AR010358-21). Retrieved via MORVS 2026-10-24 from https://api.morvs.ai/grant/nih/3154685. Licensed CC0.

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