Page 104 - Nanotechnology an introduction

More debatable is whether self-assembly offers a viable route to creating artificial cells for photovoltaic solar energy conversion. The natural system
comprises the photosystems embedded within the chloroplast, whose maintenance requires the rest of the machinery of the cell, and whose
effective operation requires a macroscopic structure of the plant (stem and branches) to support the leaves in which the chloroplasts are
embedded. The classical artificial system is the semiconductor photovoltaic cell. Can its efficiency, as well as ease of manufacture, be enhanced
by using nanostructured photoactive components? Most appraisals of the photovoltaic cell as a “renewable” or “sustainable” energy source pay
scant regard to the entire manufacturing cycle, and the key question of working lifetime under realistic conditions is scarcely addressed by
laboratory trials. Given the history of considerable efforts to more closely mimic the molecular machinery of the natural photosystems in a
nanoconstruction, it has been natural to look at extending the mimicry beyond discrete components to systems. Nevertheless, except for the
ultimate, and still hypothetical, stage of molecularly manufactured nanosystems, none of the proposed solutions comes anywhere near the
performance (considered as an overall system) of natural photosynthesis, which can simply be left to grow over vast areas (provided water is
available).

The observation that preassembled bacteriophage components (head, neck and legs) could be mixed in solution exerted a profound inspiration on
the world of “shake and bake” advocates. These components are essentially made up of proteins—heteropolymers made from irregular sequences
(α)
chosen from the 20 natural amino acids of general formula H N–C HR–COOH, where R is naturally one of 20 different side chains (residues),
2
ranging from R=H in glycine, the simplest amino acid, to elaborate heterocycles such as R=CH –[C NH ] in tryptophan. The conformation and
2
8
6
hence affinity of a protein depends on environmental parameters such as the pH and ionic strength of the solution in which it is dissolved, and this is
one mechanism for achieving programmability in assembly, since the local pH and ion concentration around a protein molecule depend on the
amino acids present at its surface. These factors also determine the conformation of the highly elongated, so-called fibrous proteins such as
fibronectin, now known to consist of a large number of rather similar modules strung together (the “daisy chain” or “pearl necklace” model). Some
other examples of biological self-assembly have already been mentioned in Section 8.2.8. A further one is provided by the remarkable S-layers
with which certain bacteria are coated. One should also mention the oligopeptides found in fungi (e.g., alamethicine) and the stings of bees
(mellitin) and wasps (mastoparan) that self-assemble into pores when introduced into a bilayer lipid membrane. But, biological self-assembly and
self-organization is by no means limited to the molecular scale (see Section 8.2.12).
8.2.11. Biopolymer Folding

Biopolymer “folding” means the transformation of a linear polymer chain, whose monomers are connected only to their two nearest neighbors, and
which adopts a random coil in solution, into a complex three-dimensional structure with additional (hydrogen) bonds between distant monomers.
Predicting the final three-dimensional structure is prima facie a difficult problem. Energetics are clearly involved, because bonds between distant
monomers form spontaneously (if geometric constraints are satisfied), releasing enthalpy and hence lowering the free energy. On the other hand,
this raises the entropy because the chain becomes constrained. Finding the free energy minimum by systematically searching configuration space
is a practically impossible task for a large molecule with thousands of atoms—it would take longer than the age of the universe. Since the protein
molecule can fold within seconds, it seems clear that the solution to the problem lies in determining the pathways. The Principle of Least Action
(PLA) is useful for this purpose: the most expedient path is found by minimizing the action.

Action is the integral of the Lagrangian for conservative systems, where L and F are respectively the kinetic and potential energies).
Minimization of the action is an inerrant principle for finding the correct solution of a dynamical problem; the difficulty lies in the fact that there is no
general recipe for constructing .
A solution leading to a successful algorithm has been found for the folding of ribonucleic acid (RNA) [52]. Natural RNA polymers are made up from
four different “bases”, A, C, G and U (see Section 4.1.4). As with DNA, multiple hydrogen bonding favors the formation of G–C and A–U pairs,
which leads to the appearance of certain characteristic structures. Loop closure is considered to be the most important folding event. F (the
potential) is identified with the enthalpy; that is, the number n of base pairings (contacts); and L corresponds to the entropy. At each stage in the
folding process, as many as possible new favorable intramolecular interactions are formed, while minimizing the loss of conformational freedom
(the principle of sequential minimization of entropy loss, SMEL). The entropy loss associated with loop closure is ΔS loop (and the rate of loop
closure ~ exp(ΔS loop )); the function to be minimized is therefore exp(−ΔS loop /R)/n, where R is the universal gas constant. A quantitative expression
for ΔS loop can be found by noting that the N monomers in an unstrained loop (N ≥ 4) have essentially two possible conformations, pointing either
inwards or outwards. For loops smaller than a critical size N , the inward ones are in an apolar environment, since the nano-enclosed water no
0
longer has bulk properties, and the outward ones are in polar bulk water. For N < N , ΔS loop = −RN ln 2 (for N > N , the Jacobson–Stockmayer
0
0
approximation based on excluded volume yields ΔS loop ~ R ln N).
In summary, SMEL applied to biopolymer folding is a least-action principle that involves sequentially maximizing the number of contacts while
minimizing entropy loss.

A similar approach can be applied to proteins [53]. However, in proteins the main intramolecular structural connectors (apart from the covalent
bonds between successive amino acid monomers) are the backbone hydrogen bonds, responsible for the appearance of characteristic structures
such as the alpha helix but which, being single, are necessarily weaker than the double and triple hydrogen bonds in DNA and RNA. They therefore
need to be protected from competition for hydrogen bonding by water, and this can be achieved by bringing amino acids with apolar residues to
surround the hydrogen bonds [54]. This additional feature, coupled with the existence of multiple conformational states already referred to (Section
8.2.8) means that proteins are particularly good for engaging in programmable self-assembly, a possibility that is, of course, abundantly made use
of in nature.

8.2.12. Biological Growth

The development of an embryo consisting of a single cell into a multicellular organism is perhaps the most striking example of self-organization in
the living world. The process of cell differentiation into different types can be very satisfactorily simulated on the basis of purely local rules enacted