Mechano-induced homotypic patterned domain formation by monocytes

Area of Science:

• Cellular and Molecular Biology
• Biophysics
• Immunology

Background:

• Matrix stiffness influences cell behavior and function through mechano-signaling.
• The impact of tissue stiffness on monocyte collective behavior and domain formation is not well understood.

Purpose of the Study:

• To investigate how physiological matrix stiffness affects human primary monocyte behavior.
• To explore the mechanisms underlying monocyte collective cell behavior and domain formation.
• To compare monocyte domain formation with other immune cells.

Main Methods:

• Utilized tunable collagen-coated hydrogels with physiological stiffness.
• Observed monocyte behavior using microscopy and developed a computational model.
• Investigated the roles of β2 integrin, soluble inhibitory factors, and cell migration.

Main Results:

• Human primary monocytes form regular, reversible, multicellular, multi-layered domains on soft matrices via local phase separation.
• Domain formation is initiated by β2 integrin activation and maintained by global inhibitory factors.
• Monocyte domain formation is unique among immune cells and promotes cell survival by inhibiting phagocytosis.
• A computational model based on phase separation and Turing mechanisms accurately predicted domain pattern formation.

Conclusions:

• Monocytes can generate complex collective cell phases by exploiting mechanosensing and signaling.
• This self-organization strategy enhances monocyte survival, distinct from active matter behavior.
• The findings reveal a novel mechanism of cell survival and collective behavior in innate immune cells.