Substrate elasticity regulates the behavior of human monocyte-derived macrophages

Adlerz, Katrina; Aranda‐Espinoza, Helim; Hayenga, Heather N.

doi:10.1007/s00249-015-1096-8

Cited by 112 publications

(100 citation statements)

References 37 publications

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“…The macrophages on stiff PDMS surfaces moved faster, showed longer movement tracks, and the cells were more spread than those on soft PDMS surfaces. These results are consistent with the report of Blakney et al (2012), that the macrophages on stiff PEG hydrogel (840 kPa) are more spread than those on soft PEG hydrogel (130 kPa); and the report of Adlerz et al (2016), which showed that the human monocyte-derived macrophages moves faster on stiff polyacrylamide hydrogel (280 kPa) than soft polyacrylamide hydrogel (3 kPa), although the materials and the ranges of stiffness are different from our study. While previous works on the effects of surface stiffness on macrophages focus on hydrogels, our results show that macrophages are also more active in the presence of E. coli biofilm cells on hydrophobic PDMS surfaces.…”

Section: Discussionsupporting

confidence: 92%

Phagocytosis of Escherichia coli biofilm cells with different aspect ratios: a role of substratum material stiffness

Zhao

Song

Wang

et al. 2017

Appl Microbiol Biotechnol

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Bacterial biofilms play an important role in chronic infections due to high-level tolerance to antibiotics. Thus, it is important to eradicate bacterial cells that are attached to implanted medical devices of different materials. Phagocytosis is a key process of the innate immunity to eliminate invading pathogens. Previous research demonstrated that the efficiency of phagocytosis is affected by the aspect ratio of polymer beads. Recently, we reported that the stiffness of polydimethylsiloxane (PDMS) influences Escherichia coli biofilm formation, and the biofilm cells on stiff (5:1) PDMS are 46.2% shorter than those on soft (40:1) PDMS. Based on these findings, we hypothesized that E. coli cells attached on stiff PDMS can be more effectively removed via phagocytosis. This hypothesis was tested in the present study using viability assays, flow cytometry and cell tracking. The results revealed that shorter E. coli cells detached from stiff PDMS were easier to be phagocytized than the longer cells from soft PDMS surfaces. Furthermore, macrophage cells were found more motile on stiff PDMS surfaces and more effective at phagocytosis of E. coli cells attached on these surfaces. These results may help the design of better biomaterials to reduce fouling and associated infections.

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Section: Discussionsupporting

confidence: 92%

Phagocytosis of Escherichia coli biofilm cells with different aspect ratios: a role of substratum material stiffness

Zhao

Song

Wang

et al. 2017

Appl Microbiol Biotechnol

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“…Furthermore,m echanical flexibility of exogenous elements within cells could be acritical design parameter toward engineering organic intracellular constructs to endow cells with unnatural yet stable and beneficial features for therapeutic applications.F inally,v iscoelasticity,p ressures and connected mechano-transductive elements are connected to inflammatory cell phenotypes. [45][46][47][48][49] As such, the mechanochemical characterization of intracellular properties could be important for cell-based mechano-biological applications leading to an ew class of pharmaceutics:m echano-pharmaceutics.…”

Section: Angewandte Chemiementioning

confidence: 99%

Elasticity in Macrophage‐Synthesized Biocrystals

et al. 2017

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Supramolecular crystalline assembly constitutes a rational approach to bioengineer intracellular structures. Here, biocrystals of clofazimine (CFZ) that form in vivo within macrophages were measured to have marked curvature. Isolated crystals, however, showed reduced curvature suggesting that intracellular forces bend these drug crystals. Consistent with the ability of biocrystals to elastically deform, the inherent crystal structure of the principal molecular component of the biocrystals – the hydrochloride salt of CFZ (CFZ-HCl) – has a corrugated packing along the (001) face and weak dispersive bonding in multiple directions. These characteristics were previously found to be linked to the elasticity of other organic crystals. Internal stress in bent CFZ-HCl led to photoelastic effects on the azimuthal orientation of polarized light transmittance. We propose that elastic, intracellular crystals can serve as templates to construct functional microdevices with different applications.

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“…In previous studies on hour timescales, anti-SIRPα increased phagocytosis of Ab-opsonized targets both in vitro [7, 15] and in vivo [10], but macrophage trafficking and function for days or weeks in the more biological contexts of circulation and 3D tissue microenvironments present a distinct challenge. On long timescales, in vitro differentiation of macrophages [16, 17] and other adherent marrow cells [18, 19] is modulated by the stiffness of their microenvironments among other factors, but in vivo evidence is lacking. We use human solid tumor models established in NSG mice (non-obese diabetic/ severe combined IL-2Rγ mice), which lack T cells, B cells (and Abs), and natural killer (NK) cells while maintaining functional monocytes, macrophages, and neutrophils [20].…”

Section: Introductionmentioning

confidence: 99%

SIRPA-Inhibited, Marrow-Derived Macrophages Engorge, Accumulate, and Differentiate in Antibody-Targeted Regression of Solid Tumors

et al. 2017

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SUMMARY Marrow-derived macrophages are highly phagocytic, but whether they can also traffic into solid tumors and engulf cancer cells is questionable, given the well-known limitations of tumor-associated macrophages (TAMs). Here, SIRPα on macrophages from mouse and human marrow was inhibited to block recognition of its ligand, the “marker of self” CD47 on all other cells. These macrophages were then systemically injected into mice with fluorescent human tumors that had been antibody targeted. Within days, the tumors regressed, and single-cell fluorescence analyses showed that the more the macrophages engulfed, the more they accumulated within regressing tumors. Human-marrow-derived macrophages engorged on the human tumors, while TAMs were minimally phagocytic, even toward CD47-knockdown tumors. Past studies had opsonized tumors in situ with antibody and/or relied on mouse TAMs but had not injected SIRPα-inhibited cells; also, unlike past injections of anti-CD47, blood parameters remained normal and safe. Consistent with tumor-selective engorge-and-accumulate processes in vivo, phagocytosis in vitro inhibited macrophage migration through micropores that mimic features of dense 3D tissue. Accumulation of SIRPα-inhibited macrophages in tumors favored tumor regression for 1–2 weeks, but donor macrophages quickly differentiated toward non-phagocytic, high-SIRPα TAMs. Analyses of macrophages on soft (like marrow) or stiff (like solid tumors) collagenous gels demonstrated a stiffness-driven, retinoic-acid-modulated upregulation of SIRPα and the mechanosensitive nuclear marker lamin-A. Mechanosensitive differentiation was similarly evident in vivo and likely limited the anti-tumor effects, as confirmed by re-initiation of tumor regression by fresh injections of SIRPα-inhibited macrophages. Macrophage motility, phagocytosis, and differentiation in vivo are thus coupled.

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Substrate elasticity regulates the behavior of human monocyte-derived macrophages

Cited by 112 publications

References 37 publications

Phagocytosis of Escherichia coli biofilm cells with different aspect ratios: a role of substratum material stiffness

Phagocytosis of Escherichia coli biofilm cells with different aspect ratios: a role of substratum material stiffness

Elasticity in Macrophage‐Synthesized Biocrystals

SIRPA-Inhibited, Marrow-Derived Macrophages Engorge, Accumulate, and Differentiate in Antibody-Targeted Regression of Solid Tumors

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