Biomedical Engineering Reference
In-Depth Information
Many biomolecules can also physisorb atop each other, thus, ensuring a chemical
linkage between the bottom layer and the surface does not
necessarily
ensure a stable
coverage
either; in applications involving direct contact between the substrate and a
cell, the space between the cell membrane and the surface can be illed by proteins
secreted by the cell; severe versions of this secretion process are the basis of the
encap-
sulation
of implants by ibroblasts or the
fouling
of surfaces by bacteria.
Because biomolecules do not react with the most widely used artiicial substrates,
it is necessary to use one or more linkage groups. he chemical groups involved in
the chemisorption reaction might cross-link unwanted molecular species, which can
confound the results; this problem can be more pronounced for multistep chemical
reactions because the eiciency of a chemical reaction never reaches 100%. We will
see several examples in these pages.
In some cases, the biomolecule itself may be degraded by natural processes (e.g., cells
can secrete proteases, enzymes that degrade proteins); in that case, whether the bio-
molecule is chemisorbed or physisorbed is irrelevant.
2.1.2 Hydrophilic versus Hydrophobic
What surfaces, then, favor physisorption? A common misconception in the BioMEMS litera-
ture is that protein physisorption can be explained or predicted by some measure of the ain-
ity of the surface to
water
—a property known as
hydrophilicity
. Hydrophilicity is not really
a magnitude (only a property) but is commonly quantitatively described by the
contact angle
between a droplet and a surface, which is the angle between the tangent of the luid-air interface
and the surface at the point of contact. (Note that hydrophilicity is identiied at the interface
of three materials: water, surface, and gas.) For a given surface, the droplet of a “wetting liq-
uid” would form a contact angle smaller than 90 degrees, that is, a droplet would look like less
than half a sphere; a “nonwetting” droplet would form a contact angle larger than 90 degrees
and would look like bigger than half a sphere. A
hydrophilic surface
is one that
water
can
wet, and a
hydrophobic surface
is one that water cannot wet, although the distinction can be
fuzzy (especially for contact angles around 90 degrees) because there is a continuum of hydro-
philicities. As it turns out, maximum physisorption is observed for surfaces that are moder-
ately hydrophobic (as are most organic polymers), for which increased protein physisorption is
correlated
with increased hydrophobicity (larger contact angles). However, hydrophilicity—or,
conversely,
hydrophobicity
—alone does not
really
explain the ainity of the protein with the
surface because neither very hydrophobic (such as Telon) nor very hydrophilic surfaces (such
as gels) support protein physisorption. Clearly, a satisfactory mechanistic explanation of physi-
sorption must account for the forces that attract the biomolecule toward that surface; the ques-
tion is extremely complex because the precise structure of water at the luid-surface interface
and at the biomolecule's surface is still, ater decades of intense research, not fully understood.
2.1.3 Cell Attachment to Substrates
he molecular mechanisms by which cells recognize certain substrates as suitable for attach-
ment have largely been elucidated. Cell adhesion is mediated by cell membrane-bound recep-
tors. In particular,
integrins
, a family of heterodimeric transmembrane proteins that are
linked to the cytoskeleton on the cytoplasmic side of the membrane, recognize speciic pep-
tide sequences present in the cell-secreted ibrillar meshwork of proteins and polysaccharides
known as
extracellular matrix
(
ECM
). hus, integrins establish a mechanical link not only
between the membrane and the ECM substrate but also between the ECM and the cytoskeleton.
Moreover, integrins aggregate in organized structures termed
focal adhesions
. More impor-
tantly, in most cell types, certain biochemical signals essential for cell growth, function, and
