Biomedical Engineering Reference
In-Depth Information
What is the molecular evidence that binding between cells and DRT actually
takes place? This question will be answered below.
9.2
Specific Binding of Contractile Cells to Ligands
on the Surface of DRT
The most abundant isoform of collagen is type I, organized into supramolecular struc-
tures (fibrils, fibers) in a manner that depends on the tissue in which it is present (e.g.,
tendons, dermis, endoneurium, cornea) and regulated by other components of the ex-
tracellular matrix (ECM; Gelse et al. 2003; Canty et al. 2005). Collagen microfibrils
(pentamers) comprise collagen molecules arranged in groups of five that become
organized into much thicker fibrils and fibers, ranging in diameter between 25 and
400 nm. Thicker collagen fibrils belong to a higher structural order than the pentamer
(Yannas 1990); they are characterized by a semicrystalline structure identified by a
67-nm periodicity, commonly referred to as the collagen banding pattern. Type I col-
lagen from a variety of animal tissues has been purified and further processed for use
as a biomaterial or for in vitro assays. Detailed protocols for preparation of medical-
grade devices based on collagen scaffolds for use in regeneration of skin and periph-
eral nerves have been published (Chamberlain and Yannas 1998) See Appendix.
Collagen adhesion receptors participate in binding various types of mammalian
cells on the surface of collagen fibers. The most important of such adhesion recep-
tors are members of the integrin family (Barczyk et al. 2010; Leitinger 2011). Four
of these integrins (α1β1, α2β1, α10β1, α11β1) comprise the family of collagen-
binding integrins (CBI; Hynes 2002). The specificities of the four CBIs for col-
lagens occasionally overlap or even play contrasting roles (Znoyko et al. 2006).
Quite importantly, integrin expression depends on cell type. The α1β1 is abundant
in smooth muscle cells, mesenchymal cells, hepatic stellate cells, pericytes, bone
marrow stem cells, chondrocytes, and neuronal cells, while α2β1 is expressed in ep-
ithelia, lymphocytes, and platelets (Popova et al. 2007; Hamaia et al. 2012). There
are also several types of nonintegrin collagen receptors (Leitinger 2011).
Integrins consist of two subunits, referred to as α and β, each subunit compris-
ing four parts: head, leg, transmembrane section, and cytoplasmic domain. The α
subunits of CBI include an additional domain close to their N terminus, usually
called “I domain” (occasionally referred to as “A domain”). Binding of an integrin
on a ligand appears to be mediated entirely by the I domain of the integrin (Hynes
et al. 2002; Luo et al. 2007). The I domains have been used as markers of adhesion
ligands of the parent integrin, providing means for assay of ligands on DRT (Tzera-
nis 2013). Integrins transmit chemical information in two directions (bidirectional
signaling; Hynes 2002). In “outside-in” signaling, occurring during binding of an
integrin to an adhesion ligand located in the extracellular matrix (ECM), the signal
from the ECM-binding event is transmitted to that part of the integrin molecule
which is located inside the cell (cytosolic domain) through conformational changes
and activates downstream signal pathways. In “inside-out” signaling, the adhesive-
ness is dynamically regulated. Bidirectional signaling is considered essential for
rapid response of the cell to environmental changes (Hu and Luo 2013).
