Multiscale Model of Colorectal Cancer Using the Cellular Potts Framework

Area of Science:

• Computational biology
• Cancer research
• Multiscale modeling

Background:

• Colorectal cancer (CRC) is a leading cause of death, originating from accumulated cell mutations within the colorectal crypt.
• Multicellular modeling offers a powerful approach to represent individual cell mutations and track their effects in tumorigenesis.

Purpose of the Study:

• To develop and utilize a multicellular model for investigating the early stages of colorectal cancer (CRC).
• To explore how cellular mechanical property modifications influence mutant cell colonization within the colorectal crypt.
• To identify potential cell- and tissue-level indicators for early-stage CRC detection.

Main Methods:

• Employed the cellular Potts model (CPM), a multicellular modeling technique, to simulate crypt dynamics.
• Investigated the impact of altered cell mechanical properties and motility parameters on crypt colonization and cell distribution.
• Coupled the CPM with processes across different spatial scales to establish biologically relevant motility parameters.

Main Results:

• Demonstrated how mutant cells with altered mechanical properties can colonize the colorectal crypt.
• Revealed that mutations influence cell shape, suggesting potential diagnostic indicators for early-stage CRC.
• Identified an optimal parameter regime for CPM motility, accurately reflecting homeostatic crypt behavior.

Conclusions:

• The CPM is effective for modeling CRC onset and understanding the role of cell mechanics and shape changes.
• Cellular mechanical properties and shape alterations are critical factors in early tumorigenesis and potential diagnostic markers.
• Optimized CPM parameters provide a robust framework for simulating realistic crypt dynamics and cancer progression.