A computational study of circulating large tumor cells traversing microvessels

Area of Science:

• Biophysics
• Cancer Biology
• Computational Biology

Background:

• Circulating tumor cells (CTCs) and CTC clusters are key indicators of cancer metastasis.
• CTCs must navigate capillary beds, facing size exclusion due to their large diameters (often >20µm) compared to capillaries (~7µm).

Purpose of the Study:

• To investigate the biophysical conditions governing the capillary arrest of CTCs and CTC clusters.
• To develop a computational model for predicting CTC passage through capillaries.

Main Methods:

• Developed a custom 3D computational model simulating viscoelastic solid-fluid dynamics.
• Calculated maximal CTC diameter passable through capillaries under physiological conditions.
• Explored the relationship between capillary pressure gradient and CTC mechanical properties (size, stiffness).

Main Results:

• Large CTCs and CTC clusters can traverse capillaries if their stiffness is low.
• A 13µm CTC requires stiffness <500Pa to pass a 7µm capillary.
• At 10Pa stiffness, CTCs/clusters up to 140µm can pass.

Conclusions:

• A pressure-size-stiffness relationship for CTC capillary transit was determined.
• The computational platform can aid in studying CTC biomechanics and metastasis.
• Findings can inform the design of size-based CTC isolation technologies.