Liquid crystalline matrix-induced viscoelastic mechanical stimulation modulates activation and phenotypes of macrophage.

Abstract

Accumulating evidence indicates that the mechanical microenvironment exerts profound influences on inflammation and immune modulation, which are likely to be key factors in successful tissue regeneration. The elastic modulus (Em) of the matrix may be a useful adjustable property to control macrophage activation and the overall inflammatory response. This study constituted a series of Em-tunable liquid crystalline cell model (HpCEs) resembling the viscoelastic characteristic of ECM and explored how mechanical microenvironment induced by liquid crystalline soft matter matrix affected macrophage activation and phenotypes. We have shown that HpCEs prepared in this work exhibited typical cholesteric liquid crystal phase and distinct viscoelastic rheological characteristics. All liquid crystalline HpCE matrices facilitated macrophages growth and maintained cell activity. Macrophages in lower-Em HpCE matrices were more likely to polarize toward the pro-inflammatory M1 phenotype. Conversely, the higher-Em HpCEs induced macrophages into an elongated shape and upregulated M2-related markers. Furthermore, the higher-Em HpCEs (HpCE-O1, HpCE-H2, HpCE-H1) could coax sequential polarization states of RAW264.7 from a classically activated "M1" state toward alternatively activated "M2" state in middle and later stage of cell culture (within 3-7 days in this work), suggesting that the HpCE-based strategies could manipulate the local immune microenvironment and promote the dominance of the pro-inflammatory signals in early stages, while M2 macrophages in later stages. The liquid crystalline soft mode fabricated in this work maybe offer a new design guideline for in vitro cell models and applications.