Oujiang Laboratory; Key Laboratory of Alzheimer's Disease of Zhejiang Province, Institute of Aging, Wenzhou Medical University, Wenzhou, Zhejiang 325000, People's Republic of China.
Shenzhen Key Laboratory of Biomimetic Materials and Cellular Immunomodulation, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong 518055, People's Republic of China.
ACS Appl Mater Interfaces. 2023 Aug 2;15(30):35832-35846. doi: 10.1021/acsami.3c04692. Epub 2023 Jul 25.
Biophysical and biochemical cues modulate mammalian cell behavior and phenotype simultaneously. Macrophages, indispensable cells in the innate immune system, respond to external threats such as bacterial infections and implanted devices, undergoing the classical M1 polarization to become a pro-inflammatory phenotype. In the study, lipopolysaccharide (LPS)-induced M1 polarization was examined using RAW264.7, THP-1, and primary human PBMCs on a family of artificial extracellular matrix (ECM), named colloidal self-assembled patterns (cSAPs). The results showed that cSAPs were biocompatible, which cannot induce M1 or M2 polarization. Interestingly, specific cSAPs (e.g., cSAP3) suppress the level of M1 polarization (i.e., reduced nitric oxide production, down-regulated gene expression of iNOS, IL-6, TNF-α, IL-1β, and TLR4, and reduced proportion of CD11bCD86 cells). Transcriptome analysis showed that cell adhesion and cell-ECM interaction participated in the M1 polarization, and the mechano-sensitive genes such as PIEZO1 were down-regulated on the cSAP3. More interestingly, these genes were also down-regulated under LPS stimulation, indicating that cells became insensitive to the LPS. The abovementioned results indicate that the defined physicochemical cues can govern macrophage polarization. This study illustrates a potential surface design at biointerface, which is critical in tissue engineering and materiobiology. The outcome is also inspiring in ECM-mediated immune responses.
生物物理和生物化学线索同时调节哺乳动物细胞的行为和表型。巨噬细胞是先天免疫系统中不可或缺的细胞，对细菌感染和植入设备等外部威胁做出反应，经历经典的 M1 极化成为促炎表型。在这项研究中，使用 RAW264.7、THP-1 和原代人 PBMC 在一系列称为胶体自组装图案（cSAPs）的人工细胞外基质（ECM）上检查了脂多糖（LPS）诱导的 M1 极化。结果表明，cSAPs 具有生物相容性，不能诱导 M1 或 M2 极化。有趣的是，特定的 cSAP（例如，cSAP3）抑制 M1 极化的水平（即减少一氧化氮的产生，下调 iNOS、IL-6、TNF-α、IL-1β 和 TLR4 的基因表达，减少 CD11bCD86 细胞的比例）。转录组分析表明，细胞黏附和细胞-ECM 相互作用参与了 M1 极化，并且 cSAP3 上的机械敏感基因（如 PIEZO1）下调。更有趣的是，这些基因在 LPS 刺激下也下调，表明细胞对 LPS 变得不敏感。上述结果表明，定义明确的物理化学线索可以控制巨噬细胞极化。本研究说明了生物界面上的潜在表面设计，这在组织工程和材料生物学中至关重要。这一结果在 ECM 介导的免疫反应中也具有启示意义。
