title: Multiple types of data are required to identify the mechanisms influencing the spatial expansion of melanoma cell colonies.
abstract: BACKGROUND
  The expansion of cell colonies is driven by a delicate balance of several mechanisms including cell motility, cell-to-cell adhesion and cell proliferation. New approaches that can be used to independently identify and quantify the role of each mechanism will help us understand how each mechanism contributes to the expansion process. Standard mathematical modelling approaches to describe such cell colony expansion typically neglect cell-to-cell adhesion, despite the fact that cell-to-cell adhesion is thought to play an important role.
  
  
  RESULTS
  We use a combined experimental and mathematical modelling approach to determine the cell diffusivity, D, cell-to-cell adhesion strength, q, and cell proliferation rate, λ, in an expanding colony of MM127 melanoma cells. Using a circular barrier assay, we extract several types of experimental data and use a mathematical model to independently estimate D, q and λ. In our first set of experiments, we suppress cell proliferation and analyse three different types of data to estimate D and q. We find that standard types of data, such as the area enclosed by the leading edge of the expanding colony and more detailed cell density profiles throughout the expanding colony, does not provide sufficient information to uniquely identify D and q. We find that additional data relating to the degree of cell-to-cell clustering is required to provide independent estimates of q, and in turn D. In our second set of experiments, where proliferation is not suppressed, we use data describing temporal changes in cell density to determine the cell proliferation rate. In summary, we find that our experiments are best described using the range D=161-243μm2 hour-1, q=0.3-0.5 (low to moderate strength) and λ=0.0305-0.0398 hour-1, and with these parameters we can accurately predict the temporal variations in the spatial extent and cell density profile throughout the expanding melanoma cell colony.
  
  
  CONCLUSIONS
  Our systematic approach to identify the cell diffusivity, cell-to-cell adhesion strength and cell proliferation rate highlights the importance of integrating multiple types of data to accurately quantify the factors influencing the spatial expansion of melanoma cell colonies.
authors: Katrina K
authors: KK
authors: Treloar
authors: Mathematical Sciences, Queensland University of Technology, Brisbane, Australia. matthew.simpson@qut.edu.au.
authors: Matthew J
authors: MJ
authors: Simpson
authors: Parvathi
authors: P
authors: Haridas
authors: Kerry J
authors: KJ
authors: Manton
authors: David I
authors: DI
authors: Leavesley
authors: D L Sean
authors: DL
authors: McElwain
authors: Ruth E
authors: RE
authors: Baker
mesh_terms: D002448:Cell Adhesion / Q000187:drug effects; D002452:Cell Count; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D048429:Cell Size / Q000187:drug effects; D006801:Humans; D007700:Kinetics; D008545:Melanoma / Q000473:pathology*; D016685:Mitomycin / Q000494:pharmacology; D049490:Systems Biology / Q000379:methods*
chemical_list: D016685:Mitomycin