Biomedical Engineering Reference
In-Depth Information
homing of circulating stem cells. Avigdor et al. [34] recently demonstrated
that the adhesion receptor CD44 and its major ligand, hyaluronic acid, are
essential for the homing of hematopoietic stem cells into the bone marrow
and spleen of immunodeficient (NOD/SCID) mice. Stem cells migrating on
hyaluronic acid toward a gradient of SDF-1 acquired a spread and polarized
morphology with CD44 concentrating at the leading edge of the pseudopo-
dia. Hyaluronic acid was concluded to play a key role in SDF-1-dependent
transendothelial migration of hematopoietic stem cells and their final anchor-
age within specific niches of the bone marrow.
Likewise, spatial concentration gradients mediated by ECM biopolymers
are the base of morphogens, signaling molecules that emanate from a re-
stricted region of a tissue and spread away from their source [35]. Mor-
phogensincludemembersoftheHedgehogfamily,theWntfamily,andsome
members of the TGFß family; their gradients provide positional information
to cells in the course of development. Recently, several reports have suggested
that heparan sulfate proteoglycans determine morphogen transport and/or
signaling. In particular, ECM seems to be critical in the restricted diffusion of
morphogens in extracellular spaces, a most important mechanism by which
morphogens traffic through tissues.
Physical cues of ECM
include the spatial constraints and mechanical forces
acting on cells from the environment.
A series of classical in vitro studies of Ingber and Whitesides [36-40] had
shown that microstructuring a planar surface with an adhesive/anti-adhesive
pattern established by the localized presence/absence of physisorption of
matrix proteins was efficient to switch adherent endothelial cells from pro-
liferation to apoptosis or vasculogenesis. In these experiments cell spreading
was varied while maintaining the total cell-matrix contact area constant by
changing the spacing between multiple focal adhesion-sized islands. The re-
sults revealed that cell shape govern whether individual cells grow or die,
regardless of the type of matrix protein or antibody to integrin used to medi-
ate adhesion. The mechanism behind these findings was suggested to concern
the forces acting on the nucleus through the cytoskeleton [41, 42]. Gradual
variations in cell shape distortion was shown to switch cells between distinct
gene programs (e.g. growth, differentiation and apoptosis), and this process
was discussed as a biological phase transition producing characteristic cell
phenotypes.
Applying new concepts from nanotechnology the idea of lateral patterning
was recently extended by Spatz et al. [43, 44] to clarify the impact of distances
between adhesive ECM ligand structures on cell adhesion. To study the func-
tion behind the molecular arrangement of single integrins in cell adhesion
hexagonally close-packed rigid templates of cell-adhesive gold nanodots were
coated with cyclic RGDfK peptides by using block-copolymer micelle nano-
lithography. These dots were positioned with high precision at 28, 58, 73, and
85 nm spacing at interfaces. A separation of
>
or = 73 nm between the adhe-
