Wrong Resemblance? Role of the Immune System in the Biocompatibility of Nanostructured Materials - Harnessing Biomaterials in Nanomedicine: Preparation, Toxicity, and Applications - page 301

but also denature the protein, thereby losing its structure [34, 73].
Interestingly, recent research points to that certain receptors in the
leukocyte cell membrane may specifically recognize structurally
decayed proteins, while their structurally intact counterparts are
significantly weaker ligands [34]. Integrins, in particular those
recognizing RGD motifs, are sensitive to the structure of their target
ligands since structural changes may expose novel RGD motifs
otherwise non-accessible for binding. The mechanisms of ligand
recognition by integrins α M β 2 and α X β 2 (described above) was
demonstrated to be strongly influenced by structural integrity of
the protein when adsorbed onto surfaces [34, 37]. The denaturation
of albumin enhanced its binding to both of these receptors [33].
Surface-induced denaturation of this protein also enhanced the
production of the pro-inflammatory TNF- α by adhering leukocyte-
like cells, probably through the stronger binding to the integrins
that support signaling [74]. The surface-induced denaturation of
proteins is not only aff ected by qualitative properties of the surfaces,
e.g., hydrophobicity or electrostatic charge, but also by the amount
of protein deposited on the surface [34]. High amounts of deposited
protein protect against denaturation by limiting the contact of each
molecule with the surface, while, by contrast, coatings with low
amounts of protein destroys the structure of the adsorbed proteins.
It has been shown in several studies that nanostructuring of surfaces
indeed regulates the amount of protein adsorbed to the surface [75].
Thus, leukocyte adhesion and cytokine production are likely to play
an important role in the response nanostructured materials that is
either engineered directly to manipulate or by accident challenge
the structure of adsorbed proteins.
10.4 Conclusions
The successful application of artificial materials in the body is
dependent not only on metabolic compatibility with the human
organism but also on an absent or limited response from the
immune system. Many non-toxic molecules have been identified for
the manufacture of biocompatible materials. However, as outlined
above, while their biological origin may support a low metabolic
toxicity, the resemblance to molecules also found on the surface of
microbes induces a strong response from the immune system upon