Role of differential adhesion in cell cluster evolution: from vasculogenesis to cancer metastasis

Jaykrishna Singh, Fazle Hussain, Paolo Decuzzi

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Cell–cell and cell–matrix adhesions are fundamental to numerous physiological processes, including angiogenesis, tumourigenesis, metastatic spreading and wound healing. We use cellular potts model to computationally predict the organisation of cells within a 3D matrix. The energy potentials regulating cell–cell (JCC) and cell–matrix (JMC) adhesive interactions are systematically varied to represent different, biologically relevant adhesive conditions. Chemotactically induced cell migration is also addressed. Starting from a cluster of cells, variations in relative cell adhesion alone lead to different cellular patterns such as spreading of metastatic tumours and angiogenesis. The combination of low cell–cell adhesion (high JCC) and high heterotypic adhesion (low JMC) favours the fragmentation of the original cluster into multiple, smaller cell clusters (metastasis). Conversely, cellular systems exhibiting high-homotypic affinity (low JCC) preserve their original configuration, avoiding fragmentation (organogenesis). For intermediate values of JCC and JMC (i.e. JCC/JMC ∼ 1), tubular and corrugated structures form. Fully developed vascular trees are assembled only in systems in which contact-inhibited chemotaxis is activated upon cell contact. Also, the rate of secretion, diffusion and sequestration of chemotactic factors, cell deformability and motility do not significantly affect these trends. Further developments of this computational model will predict the efficacy of therapeutic interventions to modulate the diseased microenvironment by directly altering cell cohesion.

Original languageEnglish
Pages (from-to)282-292
Number of pages11
JournalComputer Methods in Biomechanics and Biomedical Engineering
Volume18
Issue number3
DOIs
StatePublished - Feb 7 2015

Keywords

  • cellular organisation
  • cellular potts model
  • cell–cell adhesion
  • cell–matrix adhesion
  • chemotaxis
  • pattern formation

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