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A computational approach to understand in vitro alveolar morphogenesis.
Sean H J Kim1, Wei Yu, Keith Mostov
1UCSF/UC Berkeley Joint Graduate Group in Bioengineering, University of California, Berkeley, California, United States of America.
Plos One
|March 14, 2009
Summary
Alveolar type II (AT II) cells form lung-like cysts through a unique cytogenesis process. New computational models reveal cell-level operating principles driving this self-organization, offering insights into morphogenesis.
Area of Science:
- Cell Biology
- Developmental Biology
- Computational Biology
Background:
- Primary human alveolar type II (AT II) epithelial cells form alveolar-like cysts (ALCs) in Matrigel cultures.
- ALC formation involves a unique cytogenesis mechanism distinct from other epithelial cells, without proliferation or death.
- The underlying mechanisms and cell activities during ALC formation are not fully characterized.
Purpose of the Study:
- To identify and characterize the activities and mechanisms governing AT II cell cytogenesis during ALC formation.
- To understand the decision-making processes of AT II cells regarding switching activities.
- To gain deeper insights into the fundamental features of morphogenesis in lung epithelial cells.
Main Methods:
- A rigorous, multi-attribute modeling and simulation approach was employed.
- Agent and object-oriented programming capabilities were utilized.
- In silico cells were programmed with a set of cell-level operating principles to self-organize.
Main Results:
- In silico cells, operating quasi-autonomously, self-organized to generate cystogenesis phenomena quantitatively matching in vitro observations.
- Each simulated cell autonomously updated its environmental information, reclassified its condition, and executed a single action based on axiomatic principles.
- The collective quasi-autonomous actions of individual cells were sufficient for developing stable, cyst-like structures.
Conclusions:
- The study presents a set of cell-level operating principles that successfully model ALC formation in silico.
- The findings strengthen the mapping between in silico and in vitro results at the levels of mechanisms, behaviors, and operating principles.
- The proposed in silico operating principles may have biological counterparts, suggesting a semiquantitative mapping between in silico and in vitro causal events in morphogenesis.
