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,< Gianni Orsi>,< Carmelo De Maria>,< Francesca Montemurro>,< Giovanni Vozzi> Àú | ¾ÆÁø

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2020-07-13
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The biochemistry of a system made up of three kinds of cell is virtually impossible
to work out without the use of in silico models. Here, we deal with homeostatic
balance phenomena from a metabolic point of view and we present a new
computational model merging three single-cell models, already available from our
research group: the first model reproduced the metabolic behaviour of a
hepatocyte, the second one represented an endothelial cell, and the third one
described an adipocyte. Multiple interconnections were created among these three
models in order to mimic the main physiological interactions that are known for
the examined cell phenotypes. The ultimate aim was to recreate the
accomplishment of the homeostatic balance as it was observed for an in vitro
connected three-culture system concerning glucose and lipid metabolism in the
presence of the medium flow. The whole model was based on a modular approach
and on a set of nonlinear differential equations implemented in Simulink, applying
Michaelis-Menten kinetic laws and some energy balance considerations to the
studied metabolic pathways. Our in silico model was then validated against
experimental datasets coming from literature about the cited in vitro model. The
agreement between simulated and experimental results was good and the behaviour
of the connected culture system was reproduced through an adequate parameter
evaluation. The developed model may help other researchers to investigate further
about integrated metabolism and the regulation mechanisms underlying the
physiological homeostasis.

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Á¦ 1Æí : SIMULINK ±âº»Æí
1.1 SIMULINKÀÇ ½ÃÀÛ 1
ºí·ÏÀÇ ¿¬°á 5
ºí·Ï ÆĶó¹ÌÅÍÀÇ ¼³Á¤ 7
½Ã¹Ä·¹ÀÌ¼Ç ÆĶó¹ÌÅÍ (Configuration Parameters)ÀÇ ¼³Á¤ 8
½Ã¹Ä·¹À̼ÇÀÇ ¼öÇà 9
ºí·Ï ÆĶó¹ÌÅÍÀÇ Ç¥½Ã 9
º¹¼ö µ¥ÀÌÅÍÀÇ Ç¥½Ã 11
2.2 µ¿Àû ½Ã¹Ä·¹ÀÌ¼Ç 13
ÀÌÂ÷ ¹ÌºÐ¹æÁ¤½Ä 17
¼±Çü »óź¯¼ö ¸ðµ¨ 23
DC ¸ðÅÍÀÇ ½Ã¹Ä·¹ÀÌ¼Ç 24
ÇÔ¼ö ºí·ÏÀÇ »ç¿ë 29
Â÷ºÐ¹æÁ¤½Ä(difference equation)ÀÇ ¸ðµ¨¸µ 34
Subsystem(ºÎ½Ã½ºÅÛ)ÀÇ ±¸¼º 37

Á¦ 2Æí : ¿¬±¸³í¹®
In Silico Models for Dynamic Connected Cell Cultures Mimicking
Hepatocyte-Endothelial Cell-Adipocyte Interaction Circle

1. Introduction 41
2. Materials and Methods 45
3. New and Specific Metabolic Pathways Introduced 53
4. Validation Procedure 57
5. Results and Discussion 60
6. Conclusions 68
7. Supporting Information 69
8. References 70