Measurement of cellular traction forces during confined migration

Area of Science:

• Cell biology
• Biophysics
• Biomaterials

Background:

• Cell migration through confined extracellular matrix is essential for tissue function.
• In vivo environments present complex geometric, mechanical, and chemical challenges to cell migration.
• Understanding cell propulsion strategies in varying confinements is crucial.

Purpose of the Study:

• To investigate how cells utilize propulsive strategies in geometrically, mechanically, and chemically complex environments.
• To quantify forces cells exert during transit through constricting channels.
• To elucidate the role of substrate compliance in cell migration and nuclear deformation.

Main Methods:

• Sacrificial micromolding to create polymer substrates with tunable stiffness, adhesivity, and microscale geometries.
• Live-cell imaging to observe cell behavior.
• Three-dimensional traction force microscopy to quantify cellular forces.

Main Results:

• Mesenchymal cells migrating through compliant constrictions generate inwardly directed contractile forces.
• These forces decrease the constriction size, pulling channel walls around the nucleus.
• Nuclear deformation increased in compliant constrictions, and transit time was longer compared to rigid constrictions.

Conclusions:

• Nuclear deformation during confined migration is achieved via internal cytoskeletal machinery, not substrate reaction forces.
• The study provides a framework for testing models of nuclear translocation through narrow constrictions.
• Findings offer insights into how cells select migration strategies based on physical environmental cues.