Figure 2

ISEA components and system architecture. The in silico system consists of a CULTURE and framework components. MDCK cell cultures and ISEAs are both composite systems. A CULTURE represents one in vitro cell culture. It is a composite of three object types: CELLS, MATRIX, and free space. A hexagonal grid provides the space (CULTURE space) within which components interact. CELLS are quasi-autonomous agents whose actions are driven by their internal logic and a set of axiomatic operating principles. MATRIX maps to extracellular matrix, and FREE SPACE maps to aqueous material (e.g., cyst lumen) devoid of cells and matrix. Both are passive objects. ISEA1 [9] validated for basic, target attributes of four different cell culture types: embedded, suspension, surface, and overlay. ISEA1 was revised to ISEA2, which validated for an expanded set of target attributes. The framework provides components and methods to enable semi-automatic experimentation and analysis. EXPERIMENT MANAGER is the experiment control agent. It prepares parameter files, manages experiments, and processes data. OBSERVER is a module that automatically conducts and records measurements on CULTURE. CULTURE GUI provides a graphical interface to visualize and interactively probe CULTURE during execution.