Publications by authors named "Gilbert C Walker"

146 Publications

Phytoglycogen Nanoparticles: Nature-Derived Superlubricants.

ACS Nano 2021 05 7;15(5):8953-8964. Epub 2021 May 7.

Department of Chemistry, University of Toronto, Toronto, Ontario, Canada, M5S 3H6.

Phytoglycogen nanoparticles (PhG NPs), a single-molecule highly branched polysaccharide, exhibit excellent water retention, due to the abundance of close-packed hydroxyl groups forming hydrogen bonds with water. Here we report lubrication properties of close-packed adsorbed monolayers of PhG NPs acting as boundary lubricants. Using direct surface force measurements, we show that the hydrated nature of the NP layer results in its striking lubrication performance, with two distinct confinement-controlled friction coefficients. In the weak- to moderate-confinement regime, when the NP layer is compressed down to 8% of its original thickness under a normal pressure of up to 2.4 MPa, the NPs lubricate the surface with a friction coefficient of 10. In the strong-confinement regime, with 6.5% of the original layer thickness under a normal pressure of up to 8.1 MPa, the friction coefficient was 10. Analysis of the water content and energy dissipation in the confined NP film reveals that the lubrication is governed by synergistic contributions of unbound and bound water molecules, with the former contributing to lubrication properties in the weak- to moderate-confinement regime and the latter being responsible for the lubrication in the strong-confinement regime. These results unravel mechanistic insights that are essential for the design of lubricating systems based on strongly hydrated NPs.
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http://dx.doi.org/10.1021/acsnano.1c01755DOI Listing
May 2021

Anti-leukemia effect associated with down-regulated CD47 and up-regulated calreticulin by stimulated macrophages in co-culture.

Cancer Immunol Immunother 2021 Mar 29;70(3):787-801. Epub 2020 Sep 29.

Metrology Research Centre, National Research Council Canada, 100 Sussex Drive, Ottawa, ON, K1A 0R6, Canada.

CD47 is over-expressed in Acute Myeloid Leukemia (AML) and functions as an inhibitory signal, suppressing phagocytosis by binding to signal regulatory protein α (SIRPα) on the surface of macrophages. Inhibition of CD47 restores the immune surveillance of AML cells. However, the inhibition of CD47 in AML by activated macrophages and the subsequent effects on different immune response parameters are not fully understood. Here, we demonstrate the use of a distinct co-culture method to inhibit CD47 and therefore eliminate AML cells by macrophages in vitro. Human chemically induced THP-1 macrophages were activated using different concentrations of lipopolysaccharide (LPS) and co-culturing with three AML cancer cell lines (HL-60, NB4, and THP-1), respectively, as well as normal human peripheral blood mononuclear cells (PBMC). CD47 inhibition was observed in and selective to AML but not observed in normal PBMC. Additionally, calreticulin (CRT) levels were elevated in the same cell lines simultaneously, after co-culturing with activated human macrophages, but not elevated in normal cells. We also show that the activated macrophages secreted high levels of cytokines, including IL-12p70, IL-6, and TNF-α, consistent with the elimination of AML by macrophages. Our study reveals the potential of this model for screening new drugs against AML and the possibility of using human macrophages in AML treatment in the future.
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http://dx.doi.org/10.1007/s00262-020-02728-zDOI Listing
March 2021