Nanotopography‐Induced Unfolding of Fibrinogen Modulates Leukocyte Binding and Activation

Abstract

Surface nanotopograpy has been recognized as an important regulator of cellular responses including those of immune cells, the latter being of particular importance for implantable materials since these can determine biomaterial fate. In this paper, evidence is provided that the scale of surface nanotopography modulates the conformation of attached serum proteins, which in turn controls immune cell adhesion and activation. Model surfaces of tailored nanotopography of heights of 16, 38, and 68 nm are created by covalent immobilization of gold nanoparticles to an oxazoline-rich plasma polymer film. This strategy not only produces surfaces of tailored nanofeature density but allows control of the outermost surface chemistry. Circular dichroism spectroscopy and Mac-1 positive THP-1 monocytes studies demonstrate distinct protein unfolding patterns, which upregulate or downregulate the expression of proinflammatory cytokines and cells attachment. The findings presented in this paper shed light on the missing relationship between surface nanotopography, protein unfolding, and the immune response. On the other hand, this work demonstrates the possibility to use specifically tailored surface nanotoporaphy scales to modulate and achieve desired immune responses.

Anti‐Platelet Effect Induced by Iron Oxide Nanoparticles: Correlation with Conformational Change in Fibrinogen

“…Thus, this suggests that the cleavage site would be readily available to thrombin and would support our spectrometric data highlighting a conformational change in fibrinogen, rather than its aggregation. This is also supported by literature demonstrating that nanoparticles indeed can affect fibrinogen conformation, [ 45–50 ] including iron oxide nanoparticles. [ 31 ] Accordingly, Zhang et al.…”

Modulation of Macrophages Differentiation by Nanoscale-Engineered Geometric and Chemical Features

“…All these coatings have negative surface charges in aqueous medium at physiological pH = 7.4 as Meoxpp and ODpp coatings are slightly negatively charged -18 mV and -19 mV, respectively, whereas the ACpp coatings had the highest negative charge of -28 mV (Figure S1) [44][45] . The different chemistries of the coatings result in different wetting characteristics, as indicated by water contact angles of 35 • for ACpp, 60 • for Meoxpp and 85 • for ODpp (Figure S2) 17,46 . The thickness of the plasma polymer films was tailored to be of 5 nm, in order to preserve as much as possible the original nanoporous structure.…”

“…It is well established that different surface features play a critical role in modulating inflammatory responses [13][14][15][16][17] . However, the effect of these surface features on macrophages are still not well known.…”

“…The effect of nanotopography was further modulated by the outermost surface chemistry, revealing a complex picture of mutually dependent parameters but also an opportunity to harness surface properties to design and guide inflammatory responses to biomaterials. We have also recently reported that 'hill-like' nanotopography induced conformational changes to adsorbed fibrinogen leading to unfolding and presentation of normally hidden peptide sequences that activate the MAC-1 receptor of inflammatory cells 17 .…”

“…Recent studies by our group and others have shown that macrophage adhesion, phagocytic activity and cytokine production can be modulated by using biomaterial surface properties such as chemistry and nanotopography. These engineering tools can be effectively used to modulate inflammatory responses by biomaterial surfaces with tailored properties [13][14][15][16][17] . This provides exciting opportunity for the rational design of biomedical constructs to modulate and elicit desired immunological responses.…”