Quantification of three-dimensional cell-mediated collagen remodeling using graph theory

Cemal Cagatay Bilgin, Amanda Lund, Ali Can, George E. Plopper, Bülent Yener

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Background: Cell cooperation is a critical event during tissue development. We present the first precise metrics to quantify the interaction between mesenchymal stem cells (MSCs) and extra cellular matrix (ECM). In particular, we describe cooperative collagen alignment process with respect to the spatio-temporal organization and function of mesenchymal stem cells in three dimensions. Methodology/Principal Findings: We defined two precise metrics: Collagen Alignment Index and Cell Dissatisfaction Level, for quantitatively tracking type I collagen and fibrillogenesis remodeling by mesenchymal stem cells over time. Computation of these metrics was based on graph theory and vector calculus. The cells and their three dimensional type I collagen microenvironment were modeled by three dimensional cell-graphs and collagen fiber organization was calculated from gradient vectors. With the enhancement of mesenchymal stem cell differentiation, acceleration through different phases was quantitatively demonstrated. The phases were clustered in a statistically significant manner based on collagen organization, with late phases of remodeling by untreated cells clustering strongly with early phases of remodeling by differentiating cells. The experiments were repeated three times to conclude that the metrics could successfully identify critical phases of collagen remodeling that were dependent upon cooperativity within the cell population. Conclusions/Significance: Definition of early metrics that are able to predict long-term functionality by linking engineered tissue structure to function is an important step toward optimizing biomaterials for the purposes of regenerative medicine.

Original languageEnglish (US)
Article numbere12783
Pages (from-to)1-12
Number of pages12
JournalPLoS One
Volume5
Issue number9
DOIs
StatePublished - 2010
Externally publishedYes

Fingerprint

Graph theory
collagen
Stem cells
Collagen
Mesenchymal Stromal Cells
stem cells
Collagen Type I
cells
Tissue
Biocompatible Materials
biocompatible materials
calculi
Regenerative Medicine
Calculi
Cells
extracellular matrix
cell differentiation
cooperatives
Cluster Analysis
Cell Differentiation

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Quantification of three-dimensional cell-mediated collagen remodeling using graph theory. / Bilgin, Cemal Cagatay; Lund, Amanda; Can, Ali; Plopper, George E.; Yener, Bülent.

In: PLoS One, Vol. 5, No. 9, e12783, 2010, p. 1-12.

Research output: Contribution to journalArticle

Bilgin, Cemal Cagatay ; Lund, Amanda ; Can, Ali ; Plopper, George E. ; Yener, Bülent. / Quantification of three-dimensional cell-mediated collagen remodeling using graph theory. In: PLoS One. 2010 ; Vol. 5, No. 9. pp. 1-12.
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