Molecular Design of Biological and Nano-Materials - Biomimetics: Biologically Inspired Technologies - page 239

exhibited similar nanotube structures with the opening ends clearly visible. The wall of the tube has
been determined by neutron scattering as ~5 nm, suggestive of a bi-layer structure modeled here.
It is interesting that these simple peptides surfactants can produce remarkable complex and
dynamic structures. This is another example to build materials from the bottom-up.
One may ask how could these simple peptide detergents form such well-ordered nanotubes and
nanovesicles? The answer may lie in the molecular and chemical similarities between lipids and the
peptides since both have a hydrophilic head and a hydrophobic tail. Organic detergents have been well
studied over last few decades. The key lies in the molecular packing. However, the packing between
lipids and peptides is likely to be quite different. In lipids, the hydrophobic tails pack tightly against
each other to completely displace water, without formation of hydrogen bonds at all. On the other hand,
in addition to hydrophobic tail packing between the amino acid side chains, peptide detergents also
interact through intermolecular hydrogen bonds along the backbone. Some of these peptide detergents
displayed typical beta-sheet structures, implying the backbone extended. Thus, the tails are likely
packed in the beta-sheet form with certain curvature due to the repulsion charged heads.

8.6 PEPTIDE DETERGENTS STABILIZE MEMBRANE PROTEINS AND COMPLEXES

Many grand challenges remain in the postgenomic era, one of which is the fundamental understand-
ing of membrane biology, namely, the study of the structure and function of membrane proteins, and
specifically, the elucidation of high-resolution structures of integral membrane proteins.
Nearly all cellular signal transduction cascades occur through membrane proteins (Brann, 1992;
Haga et al., 1999; Wess, 1999). All our senses including sight, smell, hearing, taste, touch, and
temperature sensing, use membrane proteins for us to communicate with the external world. Many
important drugs used as human therapeutics act through their interaction with membrane proteins. Yet,
despite much effort in last few decades, very little is known about the intricacies and function of many
membrane proteins. Thus, meticulous and systematic determination of high-resolution membrane
protein structure will not only further our understanding of proteins as a whole, but will also enhance
our knowledge of signal transduction and accelerate development of ultra-sensitive sensing devices.
Although membrane proteins are composed of approximately one-third of total cellular
proteins (Wallin and von Heijne, 1998; Loll, 2003) and carry out some of the most important
functions in cells, only ~170 membrane protein structures have been elucidated. This is in
sharp contrast to over 30,000 nonmembrane protein structures that have been solved (http://
www.rcsb.org/pdb/ ). The main reason for this delay is difficulty to purify and crystallize membrane
proteins because removal of lipids from membrane proteins affects protein solubility and conform-
ation stability. Despite a variety of detergents and lipids as surfactants being used to facilitate,
solubilize, stabilize, purify, crystallize, and manipulate the membrane proteins for over the several
decades, how detergents interact with membrane protein to impact its structure and functions and
how to choose good detergents for the right membrane proteins remain largely unknown. This is
partly due to complexity of membrane protein-detergent-lipid interactions and lack of ''magic
material'' detergents. Therefore, the need to develop new material is urgent.
Recent experiments show that these peptide detergents are excellent materials for solubilizing,
stabilizing (Kiley et al., 2005), and crystallizing several classes of diverse membrane proteins
(Figure 8.11). These simply designed peptide detergents may now open a new avenue to overcome
one of the biggest challenges in biology — to obtain large number of high-resolution structures of
membrane proteins.
Study of the membrane proteins will not only enrich and deepen our knowledge of how cells
communicate with their surroundings since all living systems respond to their environments, but
these membrane proteins can also be used to fabricate the most advanced molecular devices, from
energy harness devices, extremely sensitive sensors to medical detection devices, we cannot now
even imagine. Following nature's lead, as the late legendary Francis Crick best put it: '' You should
always ask questions, the bigger the better. If you ask big questions, you get big answers .''