Biophysical regulation of macrophages in health and disease

Abstract

Macrophages perform critical functions for homeostasis and immune defense in tissues throughout the body. These innate immune cells are capable of recognizing and clearing dead cells and pathogens, and orchestrating inflammatory and healing processes that occur in response to injury. In addition, macrophages are involved in the progression of many inflammatory diseases including cardiovascular disease, fibrosis, and cancer. Although it has long been known that macrophages respond dynamically to biochemical signals in their microenvironment, the role of biophysical cues has only recently emerged. Furthermore, many diseases that involve macrophages are also characterized by changes to the tissue biophysical environment. This review will discuss current knowledge about the effects of biophysical cues including matrix stiffness, material topography, and applied mechanical forces, on macrophage behavior. We will also describe the role of molecules that are known to be important for mechanotransduction, including adhesion molecules, ion channels, as well as nuclear mediators such as transcription factors, scaffolding proteins, and epigenetic regulators. Together, this review will illustrate a developing role of biophysical cues in macrophage biology, and also speculate upon molecular targets that may potentially be exploited therapeutically to treat disease.

<p>The Role of Autophagy in M2 Polarization of Macrophages Induced by Micro/Nano Topography</p>

“…To be specific, many reports have demonstrated that the biophysical clues such as the surface topography which the macrophages grow on is critical for polarization regulation. [4][5][6] Our previous studies also indicate that the micro/nano topography of TiO 2 nanotubular surface with ~30 nm diameter is able to induce M2 polarization and consequently influence the osseointegration in vivo. 7,8 This phenomenon has not only provided a more convenient and safe way to induce M2 polarization, but has also led to the concept of "osteoimmunity" during the designation of bone implant.…”

Unraveling the mechanobiology of immune cells

“…Macrophages fill a crucial role in the host defense to clear pathogens and maintain tissue homeostasis, which are evidently regulated by both biochemical and biomechanical cues [for reviews, see Refs. 8 , 9 , 10 , 11 ]. Firstly, like other immune cells, monocytes need to migrate to inflamed sites.…”

“…Mimicking mechanical cues that are experienced by macrophages in the lung, cyclical hydrostatic pressure initiates an inflammatory response via the mechanically activated ion channel Piezo1 [ 5 •• , for additional stretch effects on macrophages, see Ref. 10 ].…”

Biophysical and Epigenetic Regulation of Cancer Stemness, Invasiveness, and Immune Action

“…Similarly, macrophages have been extensively reported to be sensitive to ECM composition, stiffness, and topographical and adhesive cues [97]. On diverse 2D ECM-coated surfaces, macrophages adopt varied morphologies, while also demonstrating divergent potential for polarization [98].…”