3D single cell migration driven by temporal correlation between oscillating force dipoles

Cells moving in three-dimensional environments often lack clear front-to-back actin flow patterns seen in simpler systems. While some cells use actin dynamics to break symmetry, others rely on less obvious mechanisms. The scallop theorem suggests that microswimmers must break temporal symmetry to move in low Reynolds number environments. This concept has not been clearly connected to 3D cell migration. Prior research has shown that actin flow is not always necessary for cell movement. However, how cells achieve directional motion in complex matrices remains unclear. This gap motivated the investigation of alternative symmetry-breaking mechanisms. The study explores whether dipolar forces and phase shifts could drive cell migration. No prior work had resolved the role of oscillating force dipoles in 3D cell locomotion.

The aim of this research is to understand how cells achieve directional migration in 3D matrices without coherent actin dynamics. The study focuses on the role of oscillating force dipoles and their temporal correlation. The researchers propose that cells may use a mechanism similar to the Purcell scallop theorem. This involves cycles of shape changes that break temporal symmetry. The specific problem is how cells generate motion when protrusion and retraction occur at both ends. The motivation comes from the lack of clear symmetry-breaking patterns in 3D cell migration. The study tests whether dipole-driven contractions can drive directed movement. The researchers seek to confirm this mechanism through both imaging and laser-triggered experiments.

The researchers used 3D live cell imaging to track cell movement in physiological matrices. They combined this with matrix displacement visualization to detect localized contractions. A minimal model with multipolar expansion was employed to analyze force patterns. The study focused on myosin-driven force dipoles at both sides of the nucleus. These dipoles periodically pinch the surrounding matrix. The researchers examined the phase shift between front and back dipoles. This phase shift is hypothesized to be necessary for directed motion. To test this, they used laser stimulation to trigger local dipolar contractions. This allowed them to observe whether directed movement followed from controlled force patterns.

The study found that cells in 3D matrices form myosin-driven force dipoles at both sides of the nucleus. These dipoles locally and periodically pinch the matrix. The existence of a phase shift between dipoles is required for directed motion. This phase shift leads to cycles with finite area in the dipole-quadrupole diagram. These cycles are formally equivalent to the Purcell cycle in microswimmers. The researchers confirmed this mechanism by triggering local dipolar contractions with a laser. This resulted in directed cell motion. The findings show that cells control motility through synchronized dipolar forces at front and back.

The authors propose that cells achieve directional migration in 3D matrices through oscillating force dipoles. These dipoles must have a phase shift to generate motion. The mechanism is analogous to the Purcell cycle in microswimmers. The study confirms this by showing that laser-triggered contractions lead to directed movement. The findings suggest that cell motility can be controlled by manipulating dipolar forces. This opens new strategies for external control of cell motion. The authors suggest that this mechanism could inform the design of micro-crawlers. The study provides a new framework for understanding 3D cell migration.