Physical and mechanical regulation of macrophage phenotype and function

Abstract

Macrophages are tissue-resident immune cells that play a critical role in maintaining homeostasis and fighting infection. In addition, these cells are involved in the progression of many pathologies including cancer and atherosclerosis. In response to a variety of microenvironmental stimuli, macrophages can be polarized to achieve a spectrum of functional phenotypes. This review will discuss some emerging evidence in support of macrophage phenotypic regulation by physical and mechanical cues. As alterations in the physical microenvironment often underlie pathophysiological states, an understanding of their effects on macrophage phenotype and function may help provide mechanistic insights into disease pathogenesis.

Fig. 1

a Substrate topology such as micro- and nano-grooves and fibers can modulate macrophage adhesion, spreading and activation [–27]. b Scanning electron microscopy images of murine RAW264.7 macrophages cultured on 2 μm-wide gratings and planar control surfaces [25]. Scale bar 20 μm. c Brightfield images of H&E stained RAW264.7 cells seeded on poly(L-lactic acid) (PLLA) planar and micro-aligned fibrous scaffold (fiber diameter = 1.6 ± 0.25 μm) for 7 days [26]. Scale bar 45 μm

Fig. 2

a Mechanical stretch mediates macrophage morphology and activation [38, 51]. b Immunofluorescence images of control unstretched (top) and uniaxially stretched (bottom) human U937 macrophages stained for F-actin (red), vinculin (green), and nuclei (blue) [51]. c Immunofluorescent images of human peripheral blood mononuclear cell (PBMC) derived macrophages subjected to 0, 7 and 12 % strain on poly-ε-caprolactone (PCL) scaffold, and stained for M1 marker CCR7 (red), M2 marker CD163 (yellow), and dapi (blue) [41]

Fig. 3

a Cell elongation, induced by adhesive or soluble cues, modulates macrophages phenotype [53, 56]. b Immunofluorescence images of CD11b expression in microglia cells exposed to medium conditioned (CM) by mesenchymal stem cells and/or LPS (top), and their secretion of IL-6 and TNF-α, and expression of arginase-1 (bottom). Scale bar 10 μm [56]. c Phase contrast images of BMDMs on unpatterned and patterned surfaces (left), and expression of iNOS and arginase-1 in these conditions (right). Scale bar 50 μm [53]

Fig. 4

a Fluorescence images of F-actin of BMDMs on 20 μm-wide patterned fibronectin lines and unpatterned cells that are stimulated with IL-4/IL-13 or LPS/IFN-_ϒ. Scale bar 50 μm [53]. b Immunofluorescence images of wt, Rac1^−/−, Rac2^−/− and Rac1/2^−/− BMDMs stained with F-actin (red) and paxillin (green). Inserts are higher magnification images of podosomes. Scale bar 10 μm [54]. c Schematic of macrophage mechanotransduction pathway. Podosomes, which contain focal adhesion proteins, mediate macrophage adhesion and links the actin cytoskeleton to the ECM