Biomedical Engineering Reference
In-Depth Information
The realization of these biomembrane models allows funda-
mental studies of the function of integral proteins. Biomimetic
membranes are ideally suited to elucidate many problems in mo-
lecular membrane biology, by permitting a reliable and rapid func-
tional screening of a large number of mutant receptor proteins.
This will open the way to the elucidation of structure-function re-
lationships in ligand-receptor and protein-protein interactions.
Moreover, the development of biomimetic systems that incorpo-
rate therapeutically or diagnostically important natural proteins
will open the door to the realization of sensors targeting biological
analytes. Making biomembrane models sufficiently insulating and
free from pinholes and other defects that might provide preferen-
tial pathways for electron and ionic transfer across the lipid bilayer
is a particularly challenging goal in the characterization of ion
channel activity. It can be tackled by making the solid support as
smooth as possible, by using micropatterned solid-supported lipid
bilayers formed via microcontact printing on gold, or by synthesiz-
ing hydrophilic and amphiphilic spacers with an architecture that
may favor highly compact monolayers.
Many practical applications are foreseen for these sensors,
such as the detection of drug candidates modulating the function of
ion channels and pumps or targeting membrane receptors. In this
respect, there is strong need to develop novel, rapid and highly
sensitive methods for drug screening, capable of selecting and ana-
lyzing a huge number of compounds. At present, screening of
pharmacologically active compounds follows traditional proce-
dures that apply time-consuming ligand-binding studies and recep-
tor-function tests separately. Thus, for instance, the function of ion
channels and transporters is traditionally characterized in detail by
patch clamp studies, which investigate the proteins in their natural
environment, the cellular membrane. These assays are tedious to
perform and difficult to automate at high throughput, making the
investigation of many samples difficult. The lack of knowledge
about the different functions of these channels is due to a lack of
specific inhibitors, which are unavailable due to the lack of effi-
cient measuring systems. Present ligand-binding experiments iden-
tify only ligands to already known binding sites on the protein(s)
of interest and neglect other potentially more interesting sites.
Moreover, they cannot easily differentiate between agonists and
antagonists. Thus, the direct, predominantly electrochemical de-
Search WWH ::
Custom Search