Confinement by Liquid-Liquid Interface Replicates In Vivo Neutrophil Deformations and Elicits Bleb-Based Migration

Area of Science:

• Biophysics
• Cell Biology
• Biomaterials

Background:

• Leukocyte migration through interstitial spaces is crucial for immune responses.
• Existing in vitro models struggle to replicate the deformable cellular environment of tissues.
• Mechanical cues from surrounding cells significantly influence leukocyte motility.

Purpose of the Study:

• To engineer a novel in vitro system that accurately models the deformable cellular environment encountered in vivo.
• To investigate how cell-generated forces and interfacial pressures regulate leukocyte confinement and migration.
• To explore the mechanisms of force generation used by leukocytes to overcome mechanical barriers.

Main Methods:

• Construction of microchannels with a tunable liquid-liquid interface to simulate cellular confinement.
• Utilizing the liquid-liquid interface to exert confining pressures similar to those in tissues.
• Observing and analyzing leukocyte (neutrophil) migration dynamics within the engineered microchannels.
• Employing a larval zebrafish model to validate in vitro findings in a physiological context.

Main Results:

• The liquid-liquid interface deforms in response to cell-generated forces, mimicking tissue confinement.
• Pioneer cells migrating through the interface exhibit slower speeds due to greater deformation forces required.
• Motility is regulated by tunable resistive pressures controlled via interfacial curvature.
• Neutrophils utilize a bleb-based mechanism to generate forces for deforming soft barriers.

Conclusions:

• The developed liquid-liquid interface system effectively replicates cell-scale confining pressures found in soft tissue environments.
• This system allows cells to autonomously determine their confinement, providing a more physiologically relevant model.
• The findings offer new insights into the biomechanics of leukocyte migration and immune cell trafficking in vivo.