期刊
ACS NANO
卷 7, 期 11, 页码 9984-9996出版社
AMER CHEMICAL SOC
DOI: 10.1021/nn403923h
关键词
biomimetic surfaces; nanopatterning; biofunctionalization; cell adhesion; neutrophils; platelets
类别
资金
- Studienstiftung des deutschen Volkes, Fonds der Chemischen Industrie
- HBIGS (Heidelberg University)
- European Union [NMP4-LA-2009-229289, NMP3-SL-2009229294 NanoCARD]
- National Institutes of Health (USA) through the Roadmap for Medical Research [PN2 EY016586]
- Max Planck Society
Neutrophilic granulocytes play a fundamental role in cardiovascular disease. They interact with platelet aggregates via the integrin Mac-1 and the platelet receptor glycoprotein Ib alpha (GPIb alpha). In vivo, GPIb alpha presentation is highly variable under different physiological and pathophysiological conditions. Here, we quantitatively determined the conditions for neutrophil adhesion in a biomimetic in vitro system, which allowed precise adjustment of the spacings between human GPlb alpha presented on the nanoscale from 60 to 200 nm. Unlike most conventional nanopatterning approaches, this method provided control over the local receptor density (spacing) rather than just the global receptor density. Under physiological flow conditions, neutrophils required a minimum spacing of GPlba molecules to successfully adhere. In contrast, under low-flow conditions, neutrophils adhered on all tested spacings with subtle but nonlinear differences in cell response, including spreading area, spreading kinetics, adhesion maturation, and mobility. Surprisingly, Mac-l-dependent neutrophil adhesion was very robust to GPlba density variations up to 1 order of magnitude. This complex response map indicates that neutrophil adhesion under flow and adhesion maturation are differentially regulated by GPlba density. Our study reveals how Mac-1/GPlba interactions govern cell adhesion and how neutrophils process the number of available surface receptors on the nanoscale. In the future, such in vitro studies can be useful to determine optimum therapeutic ranges for targeting this interaction.
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