4.2 Article

Morphology and dynamics of tumor cell colonies propagating in epidermal growth factor supplemented media

Journal

PHYSICAL BIOLOGY
Volume 15, Issue 4, Pages -

Publisher

IOP PUBLISHING LTD
DOI: 10.1088/1478-3975/aabc2f

Keywords

epidermal growth factor; HeLa cell; colony kinetics; dynamic scaling

Funding

  1. Consejo Nacional de Investigaciones Cientificas y Tecnicas of Argentina, CONICET [PIP 0602]
  2. Comision de Investigaciones Cientificas (CIC), Pcia. Bs. As
  3. Agencia Nacional de Promocion Cientifica y Tecnologica (ANPCyT, Argentina) [PICT-163/08, PICT-2010-2554, PICT-2013-0905]
  4. Austrian Institute of Technology GmbH (AIT-CONICET Partner Group: 'Exploratory Research for Advanced Technologies in Supramolecular Materials Science') [4947/11, 3911]
  5. Universidad Nacional de La Plata (UNLP)

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The epidermal growth factor (EGF) plays a key role in physiological and pathological processes. This work reports on the influence of EGF concentration (c(EGF)) on the modulation of individual cell phenotype and cell colony kinetics with the aim of perturbing the colony front roughness fluctuations. For this purpose, HeLa cell colonies that remain confluent along the whole expansion process with initial quasi-radial geometry and different initial cell populations, as well as colonies with initial quasi-linear geometry and large cell population, are employed. Cell size and morphology as well as its adhesive characteristics depend on c(EGF). Quasi-radial colonies (QRC) expansion kinetics in EGF-containing medium exhibits a complex behavior. Namely, at the first stages of growth, the average QRC radius evolution can be described by a t(1/2) diffusion term coupled with exponential growth kinetics up to a critical time, and afterwards a growth regime approaching constant velocity. The extension of each regime depends on c(EGF) and colony history. In the presence of EGF, the initial expansion of quasi-linear colonies (QLCs) also exhibits morphological changes at both the cell and the colony levels. In these cases, the cell density at the colony border region becomes smaller than in the absence of EGF and consequently, the extension of the effective rim where cell duplication and motility contribute to the colony expansion increases. QLC front displacement velocity increases with c(EGF) up to a maximum value in the 2-10 ng ml(-1) range. Individual cell velocity is increased by EGF, and an enhancement in both the persistence and the ballistic characteristics of cell trajectories can be distinguished. For an intermediate c(EGF), collective cell displacements contribute to the roughening of the colony contours. This global dynamics becomes compatible with the standard Kardar-Parisi-Zhang growth model, although a faster colony roughness saturation in EGF-containing medium than in the control medium is observed.

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