MS05 - CDEV-07 Part 1 of 2

Modeling cell migration at multiple scales (Part 1)

Wednesday, July 16 at 10:20am

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Note: this minisymposia has multiple sessions. The other session is: and Part-2.

Jared Barber (Indiana University Indianapolis), Luoding Zhu

Description:

Cell migration is inarguably an important process as it plays a major role in embryo development, inflammation, cancer metastasis, wound healing, and other processes. It is an inherently complex multi-scale process. While most molecular parts and corresponding processes involved in cell migration are well-characterized, it is not yet clear how such parts and processes connect and interact in order to produce the migratory motion that we typically see. For this reason, research on cell migration has continued with mathematical modeling yielding major contributions on the way. To explore how part/process interactions affect migration at multiple scales, we have invited speakers to share their work with talks that use mathematical models to explore important factors for cell migration including factors on the subcellular, cellular, and collective migration scales.

Calina Copos

Northeastern University

"Migration modes of small cell groups: which forces govern their emergent movement?"

Collective cell migration is essential to many physiological and pathological processes, yet its classification remains incomplete. Focusing on cohesive cell pairs migrating on flat substrates, we identified two motility modes: the individual contributor (IC) mode, where each cell generates its own traction force dipole, and the supracellular (S) mode, characterized by a single dipole across the pair. Amoeboid Dictyostelium discoideum (Dd) cells predominantly adopt the IC mode, while mesenchymal Madin-Darby canine kidney (MDCK) cells favor the S mode. A two-dimensional biophysical model incorporating cell-cell and cell-matrix adhesions, along with boundary contractility, recapitulated these patterns. The IC mode emerged in Dd-like cells with balanced traction, whereas S mode dominated in asymmetric or MDCK-like pairs, often driven from the rear. Increasing cell-matrix adhesion promoted the IC mode in amoeboid chains but favored the S mode in MDCK-like cells. The model, extended to longer chains, offers a novel theoretical framework to study diverse collective migration behaviors.

Yuehui Xu

Indiana University Indianapolis

"A 3D Viscoelastic Model of Cell Migration with Mechanical and Adhesive Forces"

Gaining a deeper understanding of cell migration can aid in the development of treatments for a wide range of diseases in which it plays a major role, including infection and cancer. To investigate the mechanisms of cell migration and identify key factors that influence migratory behavior, we developed a three-dimensional mathematical model of an HEK 293 cell migrating unidirectionally on a flat substrate. The cell is represented as a network of viscoelastic elements, while focal adhesions are modeled as points on the cell membrane that connect to the substrate using elastic fibers. The model includes forward pushing forces that are typically generated by actin filaments and cause the cell to protrude in the migratory direction. It also includes an internal interconnected set of elements that represent the internal cell structure. We share how our approach is capable of producing results that agree qualitatively with experiment and vary simulation parameters to examine how the cell responds to changes in membrane stiffness, substrate stiffness, internal element elasticity, the number of focal adhesions, and frictional forces. Results suggest the model can be used to consider more physiologically relevant questions in the future such as the effects of different component properties on overall cell migration and forces.

John Dallon

Brigham Young University

"Modeling differential cell motion in the Dictyostelium discoideum slug"

Differential cell motion plays an important role in the front to back pattern formed during the slug stage of the organism Dictyostelium discoideum (Dd). The slug has at least two cell types: prespore cells and prestalk cells. As the slug moves the prestalk cells aggregate to the front of the moving slug while the prespore cells aggregate to the rear. In this talk I will discuss a force based mathematical model where cells attach and detach to one another via discrete adhesions with stochastic dynamics. Using simulations, different strategies that cells could employ are explored which cause differential cell motion leading to this front to back pattern.

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Annual Meeting for the Society for Mathematical Biology, 2025.