Several charges are needed on a polymer for it to overcome the dissipative tendency of thermal energy and bind to a surface.
This resembles the length requirement of an oligonucleotide to prime polymerization of the complementary DNA strand. Relatively
little heat is exchanged on binding of a polyelectrolyte to an oppositely charged surface, so ΔG≈–TΔS, where G is free energy, T is temperature (in degrees Kelvin), and S is entropy. In other words, adsorption is largely driven by an increase in entropy. This increase is as a result of the release
of small counterions to solution as side-chain charges in the newly adsorbed polymers form ion pairs with side chains of opposite
polarity on the surface of the nanofilm. A useful compendium of essays on experimental and theoretical aspects of multilayer
films is available (26), as is a brief summary of the physics of nanofilm fabrication (34).
It should be noted that the polyelectrolyte film fabrication method outlined above places no strict geometrical requirement
for the substrate. Indeed, these films have been built on substrates of varying surface roughness and shape. Spherical particles
in the nanometer to micrometer range have attracted considerable attention (27–28). There are three basic approaches with
spherical particles: coating microparticles when the particles are the material of interest (29), trapping a material of interest
that has been adsorbed onto template particles (30), and creating hollow spherical shells by dissolving the "dummy" template
particles after nanofilm fabrication for subsequent "loading" and "release" of molecules of interest (31–33). All these approaches
present interesting possibilities for systemic or local drug delivery.
The work of the author's research group has been comprehensive, encompassing the physics, chemistry, and biology of multilayer
nanofilms made of polypeptides (14, 21, 34). With regard to physics, we have investigated how the electric charge, hydrophobic
surface, and side-chain hydrogen bonds of peptide structures contribute to PMN assembly, structure, and stability (35). Amino
acid side chains have rather different chemical properties. With regard to biology, we have investigated how PMN designs influence
cell behavior in vitro and in vivo (36–37). We have been especially interested in the extent to which we can control cellular phenotype in vitro or foreign body tissue reactions in vivo by encoding biological information in peptides for PMN fabrication.
In fundamental studies of the role of electronic charge density, hydrophobic interactions, and side-chain hydrogen bonds in
PMN fabrication, structure, and stability (35), we have found that changes in peptide structure can have a surprisingly large
impact on PMN fabrication, overall nanofilm thickness, and nanofilm density for a given number of polymer-adsorption steps
during fabrication. Control over film thickness and density are potentially useful for determining the ability of the film
to act as a diffusive barrier, which can provide differential controls over the rate of release of encapsulated materials
(see Figure 2). We have validated PMN fabrication on a wide range of substrates with widely ranging electronic properties.
We have also explored coding regions of the human genome for sequences that are suitable for PMN fabrication (38). These sequences
will generally have a large number of charged side chains per residue and a large net charge at neutral pH. Both conditions
are needed for control over peptide solubility and binding affinity in PMN. Such sequence information is also potentially
useful for controlling the immunogenicity of individual peptides and PMNs. PMNs intended for contact with blood, for instance,
could be designed using sequence information from known blood proteins, tested experimentally, and modified as needed to achieve
the desired properties.