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Viscoelastic modeling of the fusion of multicellular tumor spheroids in growth phase.
Dechristé, Guillaume; Fehrenbach, Jérôme; Griseti, Elena; Lobjois, Valérie; Poignard, Clair.
Afiliação
  • Dechristé G; Team MONC, INRIA Bordeaux-Sud-Ouest, CNRS UMR 5251, 351 cours de la Libération, Talence Cedex 33405, France. Electronic address: guillaume.dechriste@gmail.com.
  • Fehrenbach J; Université de Toulouse, ITAV, CNRS, Toulouse, France. Electronic address: jerome.fehrenbach@math.univ-toulouse.fr.
  • Griseti E; Université de Toulouse, ITAV, CNRS, Toulouse, France. Electronic address: elena.griseti@ipbs.fr.
  • Lobjois V; Université de Toulouse, ITAV, CNRS, Toulouse, France. Electronic address: Valerie.lobjois@itav.fr.
  • Poignard C; Team MONC, INRIA Bordeaux-Sud-Ouest, CNRS UMR 5251, 351 cours de la Libération, Talence Cedex 33405, France. Electronic address: clair.poignard@inria.fr.
J Theor Biol ; 454: 102-109, 2018 10 07.
Article em En | MEDLINE | ID: mdl-29775683
ABSTRACT

BACKGROUND:

Since several decades, the experiments have highlighted the analogy of fusing cell aggregates with liquid droplets. The physical macroscopic models have been derived under incompressible assumptions. The aim of this paper is to provide a 3D model of growing spheroids, which is more relevant regarding embryo cell aggregates or tumor cell spheroids.

METHODS:

We extend the past approach to a compressible 3D framework in order to account for the tumor spheroid growth. We exhibit the crucial importance of the effective surface tension, and of the inner pressure of the spheroid to describe precisely the fusion. The experimental data were obtained on spheroids of colon carcinoma human cells (HCT116 cell line). After 3 or 6 days of culture, two identical spheroids were transferred in one well and their fusion was monitored by live videomicroscopy acquisition each 2 h during 72 h. From these images the neck radius and the diameter of the assembly of the fusing spheroids are extracted.

RESULTS:

The numerical model is fitted with the experiments. It is worth noting that the time evolution of both neck radius and spheroid diameter are quantitatively obtained. The interesting feature lies in the fact that such measurements characterise the macroscopic rheological properties of the tumor spheroids.

CONCLUSIONS:

The experimental determination of the kinetics of neck radius and overall diameter during spheroids fusion characterises the rheological properties of the spheroids. The consistency of the model is shown by fitting the model with two different experiments, enhancing the importance of both surface tension and cell proliferation. GENERAL

SIGNIFICANCE:

The paper sheds new light on the macroscopic rheological properties of tumor spheroids. It emphasizes the role of the surface tension and the inner pressure in the fusion of growing spheroid. Under geometrical assumptions, the model reduces to a 2-parameter differential equation fit with experimental measurements. The 3-D partial differential system makes it possible to study the fusion of spheroids in non-symmetrical or more general frameworks.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Esferoides Celulares / Proliferação de Células / Modelos Teóricos / Neoplasias Limite: Humans Idioma: En Revista: J Theor Biol Ano de publicação: 2018 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Esferoides Celulares / Proliferação de Células / Modelos Teóricos / Neoplasias Limite: Humans Idioma: En Revista: J Theor Biol Ano de publicação: 2018 Tipo de documento: Article