Molecular self-assembly in a model amphiphile system
Lorna Dougan
Introduction
Biological processes are intimately linked to the unique properties of water and the versatility
with which it interacts with a wide variety of biomolecules. These interactions are thought to
be of major significance in the structure, dynamics and activity of proteins, the formation of
biological membranes and the transport of ions and co-solutes. Of particular interest is water’s
behaviour with respect to non-polar molecules or non-polar groups of biomolecules, which
have a tendency to adhere to each-other to minimize their exposure to the solvent. The
process by which molecules containing both non-polar and polar regions adopt a defined
arrangement is termed molecular self-assembly. Given the complexity of typical biological
self-assembly systems it is useful to consider a model system which retains the key elements
of interest for the study of self-assembly. One such model system are the alcohols which
contain both a polar group (OH) and non-polar methyl groups (CH3) and offer the opportunity
to study the properties of a small amphiphile in an aqueous environment.
Beyond the ‘iceberg’ model
The thermodynamic signatures associated with the hydration of alcohols are striking. When
water is mixed with an amphiphilic molecule, the entropy of mixing is non-ideal. In fact the
excess entropy is frequently negative, as occurs in the instance of methanol in water.
Historically, the most familiar and favoured explanation for this general behaviour has been
based on the notion of enhanced water ordering in the vicinity of hydrophobic groups.
According to this model, the structural enhancement of solvent explains the negative
deviation from ideal entropy of mixing and thereby leads to an entropic driving force for
hydrophobic association of non-polar groups. Despite the attractiveness of this description, its
validity has now been questioned by a number of diffraction measurements which report no
discernible structural enhancement of water near non-polar groups. In a recent paper we
showed that the excess entropy could be quantitatively explained in terms of a simple model
which explores the observed partial molecular-scale demixing of alcohol and water in solution.
It does this without resort to the idea that water is more structured around the hydrophobic
headgroups, the so-called “iceberg” model. This work suggested that it is the amphiphilic
nature of a molecule that determines the self-assembly process in aqueous solution. In the
present study we continue this theme, invoking recent data on the effect of temperature and
pressure on the mixing of alcohol-water.
This approach now presents an attractive framework for examining the behaviour of model
amphiphile systems under cooling and compression. Given the important contributions of
both enthalpic and entropic contributions to the self-assembly of biological systems, use of a
simple model system allows detailed examination of the interplay between molecular selfassembly and thermodynamics. In this study we extend our analysis to methanol-water
mixtures far from ambient conditions to separate the effects of pressure and temperature on
the excess entropy. This allows us to draw conclusions about the clustering behaviour in this
important model system. Furthermore, by studying a model amphiphile system we have the
possibility of making predictions about the behaviour of biological amphiphile systems of
greater complexity.
Our results suggest that under increased pressure and reduced temperature, the average cluster
size of both water and methanol clusters, while the system becomes better mixed. This
apparent contradiction can be explained by a change in topology of the clusters, with water
clusters becoming more sheet-like, rather than globular, and hence interacting more with the
surrounding methanol clusters. This work suggests that structural properties of a system,
driven by molecular self-assembly, determine the thermodynamics. Ongoing work will
examine the molecular self-assembly of cryoprotectant aqueous solutions which exhibit
interesting thermodynamic properties.
Figure 1: self-assembly of water and methanol in the liquid state. The schematics of two models are
shown in (A) and (B). In (A) the ‘fully demixed’ model there is a sharp boundary between the water and
alcohol clusters, depicted in the schematic as 1 and 2. There is no mixing at the atomic level. In (B) the
‘interface’ model water and alcohol again exist at clusters but there is now an interfacial region containing
both water and alcohol. The molecules assigned to the interface are treated as randomly mixed and so make
negligible contribution to the excess entropy of the system. The entropy of the system is determined not only
by the size of the clusters but also by their topology and the topology of the interfacial region. (C) Neutron
diffraction data coupled with computational modelling allows for examination of the clustering of water and
alcohol. Applying the ‘interface’ model we can accurately calculate the excess entropy of the system, which
is in good agreement with experimental data. This approach shows that structural insight into a system can
provide an insight into important thermodynamic properties of a system. Publications
Dougan, L., Crain, J., Finney J. & Soper A. (2010) Molecular self-assembly in a model amphiphile
system, Phys. Chem. Chem. Phys. 12:10221 -10229.
Funding
This work is funded by EPSRC (2010-EP/H020616/1)
Collaborators
Prof. Alan Soper, Rutherford Appleton Laboratories, United Kingdom
Prof. John Finney, University College London, United Kingdom