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Defined Surface Physicochemical Cues Inhibit M1 Polarization of Human Macrophages Using Colloidal Self-Assembled
Jia-Nan Song1, Kun Liu2, Jie Mei1,3,4,5,6
1Oujiang Laboratory; Key Laboratory of Alzheimer's Disease of Zhejiang Province, Institute of Aging, Wenzhou Medical University, Wenzhou, Zhejiang 325000, People's Republic of China.
ACS Applied Materials & Interfaces
|July 25, 2023
Summary
Artificial extracellular matrix (ECM) patterns can control macrophage polarization, a key immune response. Specific patterns suppressed pro-inflammatory M1 polarization, offering insights for biomaterials and tissue engineering.
Area of Science:
- Biomaterials Science
- Immunology
- Cell Biology
Background:
- Mammalian cell behavior is influenced by biophysical and biochemical cues.
- Macrophages are crucial innate immune cells that polarize to M1 (pro-inflammatory) or M2 phenotypes in response to stimuli.
- Understanding macrophage polarization is vital for applications in tissue engineering and immune response modulation.
Purpose of the Study:
- To investigate the effect of colloidal self-assembled patterns (cSAPs), a novel artificial extracellular matrix (ECM), on macrophage polarization.
- To determine if cSAPs can modulate lipopolysaccharide (LPS)-induced M1 polarization in macrophage cell lines and primary cells.
- To explore the underlying mechanisms, including cell adhesion, ECM interaction, and mechano-sensitive gene expression.
Main Methods:
- Utilized RAW264.7, THP-1, and primary human peripheral blood mononuclear cells (PBMCs).
- Cultured cells on various cSAPs and assessed M1 polarization markers (nitric oxide production, gene expression of iNOS, IL-6, TNF-α, IL-1β, TLR4, and cell surface markers CD11b+/CD86+).
- Performed transcriptome analysis to identify affected pathways and genes, including mechano-sensitive genes like PIEZO1.
Main Results:
- cSAPs demonstrated biocompatibility without inducing M1 or M2 polarization on their own.
- Specific cSAPs (cSAP3) significantly suppressed LPS-induced M1 polarization, reducing nitric oxide production and down-regulating key pro-inflammatory genes.
- Transcriptome analysis revealed that cell adhesion and ECM interaction pathways were involved, with mechano-sensitive genes like PIEZO1 being downregulated on cSAP3 and also under LPS stimulation, suggesting altered cellular sensitivity.
Conclusions:
- Defined physicochemical cues of artificial ECM can effectively govern macrophage polarization.
- Specific cSAP designs can suppress pro-inflammatory M1 macrophage polarization, presenting a potential strategy for biointerface design.
- Findings offer insights into ECM-mediated immune responses and have implications for biomaterial development in tissue engineering and materiobiology.
