Download Molecular Self-Assembly

NUE: Lab-on-a-chip Nanomanufacturing in Freshman Engineering
Tomasko/Merrill/Stevenson
Molecular Self-Assembly
Professor Jim F. Rathman, Department of Chemical Engineering
Learning Objectives
This module will introduce students to:
• Role of intermolecular forces in molecular self-assembly of amphiphilic molecules.
• Formation of 3-D structures by self-assembly in solution
• Surface tension and the formation of 2-D structures by self-assembly at interfaces
Introduction
Self-assembly is the process in which molecules or molecular aggregates spontaneously
organize into 2- or 3-dimensional structures. The forces involved in self-assembly are much
weaker than the relatively strong forces involved in covalent chemical bonds. The organization
of a selfassembled structure is maintained by a balance of weaker intermolecular forces. These
forces include hydrogen bonding, Coulombic (electrostatic) interactions, coordination bonding,
and van der Waals interactions. For example, self-assembly of soap molecules in water
involves both hydrophobic forces, which tend to promote aggregation, and hydrophilic
interactions, which favor the dispersion of molecules. Since the majority of self-assembly
processes involve nanometer-sized entities, external effects such as capillary forces, electric or
magnetic fields, and flow can strongly influence the self-assembly process. Although scientific
knowledge in this area has a long history, interest in molecular self-assembly has dramatically
increased in recent years. Exciting new techniques have been developed that allow us to
actually manipulate individual molecules or clusters of molecules. For this reason, selfassembly is key to “bottom-up” strategies in the nanomanufacturing of novel materials and
devices.
Biological systems provide numerous examples of self-assembled structures. Many essential
life activities are strongly controlled and regulated by self-assembly. Due to the relatively weak
interactions involved, a self-assembled structure is much more sensitive and responsive to its
environment than a more rigid structure held together by covalent bonds. Self-assembly
processes in biological systems are usually directional and functional, and often lead to the
formation of extremely complex structures. For example, the three-dimensional structure
adopted by a protein in solution is critical to the protein’s function, and this structure is
determined by both strong (covalent) and weak interactions. Thanks to the weaker interactions,
the protein can respond dynamically to changes in its environment.
The wide spectrum of self-assembly phenomena can be categorized in various ways. In this
module, we will discuss the similarities and differences between 2- and 3-dimensional systems.
We will also discuss applications of self-assembly processes.
Fundamentals
Intermolecular forces. In order to understand the process of self-assembly, we need to start by
thinking about the types of interactions that may occur between two molecules. The strongest
interaction is the special case in which a covalent bond forms between the molecules – we call
NUE: Lab-on-a-chip Nanomanufacturing in Freshman Engineering
Tomasko/Merrill/Stevenson
this a “chemical reaction” and the result is that we no longer have two distinct molecules, but
rather a new molecule. We are not interested in chemical reactions here because self-assembly
generally involves much weaker types of interactions. Charge-charge (Coulombic) interactions
are important when ionic molecules are involved: attractive interactions result when the
molecules are oppositely-charged, and repulsive interactions occur when the molecules are either
both positive or both negative. Coulombic interactions are also important when non-ionic polar
molecules are involved. The electrons in a polar molecule are not uniformly distributed, so
although the molecule has no net charge one portion of the molecule has a slight negative charge
while another portion is slightly positive. When two polar molecules come into close proximity,
an attractive interaction can develop as the positively-charged region in one molecule interacts
with the negatively-charged region of the second molecule. Interestingly, attractive interactions
also arise between molecules that are non-ionic and non-polar. On average, the electrons are
distributed uniformly within these molecules; however, at any given instant the electrons may be
non-uniformly distributed due to their random and chaotic movement. This effect is enhanced
when another molecule comes close to the first molecule – the dynamic fluctuations in electron
distributions in one molecule are influenced by the fluctuations in the other molecule. The net
result of all this chaos turns out to be an attractive interaction that we call van der Waals forces.
Thanks to the van der Waals interactions, attractive interactions occur between any two
molecules, even for example two molecules of an “inert” substance such as helium.
Amphiphilic molecules. Molecules that are “amphiphilic” are especially important in selfassembly. An amphiphilic molecule is one in which part of the molecule is chemically similar to
the solvent in which the molecule is placed while another part of the molecule is chemically
incompatible with the solvent. Did you brush your teeth this morning? If so, then your toothpaste
probably contained sodium dodecylsulfate, an amphiphilic molecule that has a hydrophilic
(“water-loving”) head group and hydrophobic (“water-fearing”) hydrocarbon tail group.
Throughout the day you use many products containing amphiphilic molecules, including
surfactants (“surface-active agents”) and soaps used in cleaning products and as dispersing
agents in foods.
3-D self-assembly of surfactants. Now let’s consider what happens when we dissolve
amphiphilic molecules in water. At low concentrations a solution will contain individual
molecules of surfactant dispersed in the solvent (water). Since water is a polar solvent, the ionic
headgroup of the surfactant interacts favorably with the surrounding water molecules;
interactions between water molecules and the hydrophobic surfactant tail are also attractive, but
are much weaker. Because the hydrophobic tail disrupts the hydrogen bonding between water
molecules in this vicinity, the water molecule are packed in a highly ordered structure along the
surfactant tail. Note that the term “hydrophobic” is really not a very good description of this
interaction – the surfactant tail does not
micelle
“fear” water molecules – in fact, van der
Waals interactions result in a net attractive
interaction, but this interaction is relatively hydrophilic
head
weak and comes at the expense of breaking
some of the stronger hydrogen bonds
between
water
molecules.
If
the
hydrophobic
concentration of surfactant is increased, at
tail
2 – 5 nm
NUE: Lab-on-a-chip Nanomanufacturing in Freshman Engineering
Tomasko/Merrill/Stevenson
some point the surfactant molecules get close enough to start interacting with each other instead
of just interacting with water molecules. Although there is a repulsive interaction between
surfactant head groups, there is a strong attractive interaction between the tails. As a result,
surfactant molecules in solution will spontaneously self-assemble into aggregates (called
“micelles”) that allow for extensive interaction between their hydrophobic tails while allowing
the hydrophilic heads to remain in contact with the solvent. The water molecules also like this
process – no longer confined to being packed in orderly fashion along the hydrophobic tail of the
amphiphilic molecule, they are now free to move about the solution like normal water molecules.
This phenomena, driven by attractive tail-tail interactions and the desire of the bound water
molecules to “go free”, is called the hydrophobic effect. Depending
on properties of the amphiphilic molecule and its concentration in
solution, a rich variety of self-assembled structures can be formed.
For example, rod-shaped micelles can be formed and, at higher
concentrations, the micelles themselves aggregate to form a liquid
crystalline phase. Other types of amphiphiles, such as the lipids that
hexagonal packing
of rod-shaped micelles
form cell membranes in biological systems, tend to form bilayer
structures.
It’s useful to think about why amphiphilic molecules are so
important in the formation of self-assembled structures. What might
happen for example, in a solution containing a simple hydrocarbon
oil such as decane? Decane is not amphiphilic – it is a purely
bilayer structure
hydrophobic compound. Since there is no hydrophilic group to
interact strongly with water, it’s very difficult to dissolve a decane molecule into water; nature
doesn’t like having to break the strong hydrogen bonds between water molecules when all it gets
in return are the much weaker water-decane interactions. Decane molecules also don’t like this –
they much rather prefer interacting with other decane molecules and will therefore do so very
readily. Remember that the self-assembly of surfactant molecules is a balance between attractive
tail-tail interactions and repulsive head-head interactions. In the case of decane, there are no
repulsive interactions to counter the attractive decane-decane interactions, so an infinite number
of decane molecules can come together. We all know that “oil and water don’t mix” – this is
exactly the reason why! If we attempt to make a solution of decane in water, we end up with an
essentially pure liquid decane floating on top of an essentially pure liquid water phase. The selfassembly of a surfactant is in many ways similar to a phase separation with one very important
difference: because of the balance between hydrophilic and hydrophobic effects, the equilibrium
size of the self-assembled structure is finite, consisting of a relatively small number of
molecules. From an engineering standpoint, self-assembly of amphiphilic molecules is therefore
an extremely attractive route towards creating materials and devices with nanoscale features that
are of the same size and shape as these structures.
Self-assembly in biological systems. In addition to the hydrophobic and electrostatic forces that
are major factors in the self-assembly of surfactants and amphiphilic polymers, the formation of
self-assembled biological structures also often involves the formation of covalent bonds, such as
disulfide bonds for example. These rather strong forces provide additional driving forces for
biological self-assembly, but in many cases they act as “functional forces” as well. A variety of
vital life activities such as cell-cell interaction, intercellular aggregation, activation of the
NUE: Lab-on-a-chip Nanomanufacturing in Freshman Engineering
Tomasko/Merrill/Stevenson
cytoskeleton, transport through plasma membranes, cell fusion and lysis, focal adhesion,
formation of collagen and fibronectin networks, and movement of certain cells on solid surface
are largely due to biological self-assembly that can be understood as the hierarchical evolution of
self-assembly in nature. Due to its diversity and complexity, biological self-assembly is more
difficult to characterize than surfactant self-assembly.
Self-assembly at larger length scales. Self-assembly is not limited to molecular-scale building
blocks. Self-assembly of much larger entities is also possible, usually aided by external forces
such as capillary effects, electric and magnetic field, and shear and elongational flows. These
approaches rely on the careful design and modification of surface chemistry of the building block
objects. For example, assembly of solid objects on the millimeter-to-centimeter size into an
amazing level of hierarchy and architectural variety using lateral capillary forces has been
demonstrated. Assembly and directional orientation of liquid crystals in a magnetic field
provides another example of this category of self-assembly.
Surface tension and 2-D self-assembly. Nature doesn’t like surfaces. A water droplet falling
through the air will tend to take on a spherical shape in order to minimize the water-air surface
area. If two water droplets rolling around on a Teflon surface collide they readily coalesce to
form a single drop, again because the single drop has less exposed area than the two drops. The
tendency to minimize interfacial area is a consequence of surface tension, an important property
of liquids and solids. Although surface tension is a complex phenomena, we can start to
understand it by appreciating the fact that molecules at a surface or interface are in a different
environment than molecules inside a homogeneous bulk phase. In pure liquid water, a water
molecule in the bulk is surrounded by other water molecules, experiencing many attractive
interactions due to the strong polar nature of water. A water molecule at the air-water surface is
much less happy since there are far fewer molecules for this molecule to interact with and so
water has a rather high surface tension.
The surface tension of a liquid can be decreased significantly by the addition of amphiphilic
molecules. In addition to their self-assembly to form 3-dimensional structures in solution, these
molecules also do some very interesting things at interfaces. Surfactant molecules dissolved in
water not only may form micelles within the solution but will adsorb at the air-water interface.
Due to the favorable tail-tail interactions between adsorbed
air
surfactant molecules, surfactant molecules are much more
“comfortable” at the interface than water molecules, so the
surface tension of the solution is much lower than for pure
water. The attractive tail-tail interactions also drive the selfassembly of surfactant molecules into structured aggregates
on the surface. Since this process is confined to the interfacial
water
region, these aggregates are essentially 2-dimensional
analogs of the 3-dimensional structures formed by selfassembly in bulk solution.
Self-assembled structures formed on a liquid surface can be deposited onto a solid surface using
a process known as Langmuir-Blodgett deposition. This technique allows for a high degree of
control over the transfer process, so that the structure of extremely thin films can be preserved
NUE: Lab-on-a-chip Nanomanufacturing in Freshman Engineering
Tomasko/Merrill/Stevenson
during the transfer process. As discussed in the next section, these nanostructured thin films have
a variety of possible applications.
Examples and Applications of Molecular Self-Assembly
Biomineralization and biomimetic materials. Diatoms, animal bone, abalone shell, spider silk,
and eggshell are among the many examples of complex materials produced in nature by
biomineralization. Understanding the process by which these materials are formed will therefore
provide excellent insight for the development of new synthetic materials. The key to
biomineralization, the process in which these materials are produced in nature, is the cooperative
self-assembly between inorganic constituents and self-assembled bioorganics such as proteins,
enzymes, and membrane lipids. These self-assembled structures act as templates on which the
polymerization of reactive inorganics occurs to form the structured solid material. An important
characteristic of this process is that the self-assembly usually proceeds multi-step wise, making
the final structures highly hierarchical. Mimicking the biomineralization process in the
laboratory is believed to be a very promising and efficient route towards the discovery of new
materials with excellent mechanical, chemical, and/or electromagnetic properties.
Advanced porous materials. Examples of advanced materials produced by exploiting molecular
self-assembly include highly porous materials, magnetic fluids, and optomagnetic multilayered
films. In the production of mesoporous silica, reactive silicate species are added to a
concentrated surfactant solution. The 3-dimensional self-assembled surfactant structures act as
templates – the reaction of silicate ions to form silica occurs on the outer walls of the surfactant
aggregates. At the end of the reaction, the surfactant is removed either by solvent extraction or
calcination, leaving a remarkably porous silica product. This material can have a surface area of
more than 1000 m2 per gram, which is ideal for use as a catalyst support or adsorbent.
Ultrathin films. Applications of ultrathin films
containing 2-dimensional self-assembled structures
include sensors and scaffolds for tissue engineering.
This picture shows a 10 µm × 10 µm image, obtained
by atomic force microscopy, of a 2-dimensional
network of collagen fibers grown on a self-assembled
lipid monolayer at an air-water interface. Collagen is
the most abundant protein present in animals and plays
an important role in connective tissues and the
adhesion of cells to surfaces. This is an example in
which an extremely complex biological process, the
polymerization of collagen monomers to form a fibrous
network, has been successfully realized in an artificial
environment.
An Historical Perspective: The Amazing Agnes Pockels
Some of the most important contributions in science come from the least expected places.
Extraordinary people have accomplished remarkable things despite very limited means or
NUE: Lab-on-a-chip Nanomanufacturing in Freshman Engineering
Tomasko/Merrill/Stevenson
difficult circumstances. A prime example is the development of the technique first used to
estimate the size of a molecule and still used today to investigate the self assembly of molecules
on the surface of a liquid. This technique was developed by a woman who had only a high school
education, working in her own home with common household wares for her experimental tools,
and performed in the 1880’s, a time when many people did not even believe in the existence of
molecules. Agnes Pockels was born in 1862 and, after completing high school in Brunswick,
Germany, she dreamed of continuing her education at a university – but unfortunately she was
never able to do so:
“In high school, I had already developed a passionate interest in the natural
sciences, especially in physics, and would have liked to become a student, but at
that time women were not accepted for higher education and later on, when they
started to be accepted, my parents nevertheless asked me not to do so.”
Pockels lived at home for all of her life, finding time for her experiments while not taking care of
the house and her sickly parents. Her experiments were truly amazing! Agnes was interested in
surface tension. She was especially interested in how the surface tension of water could be
drastically changed by deposition of very tiny amounts of other materials (materials we now call
“surfactants”) onto the surface. Pockels devised a method that allowed her to deposit an
extremely tiny amount of surfactant on the surface, so that initially the number of surfactant
molecules per unit area of surface was very low. She then showed that, by sweeping a movable
barrier across the surface, the confined molecules could be concentrated into a smaller area and
that the surface tension decreased as the number of surfactants molecules per area increased.
References for Further Study:
Rajagopalan, R. “Colloids and Interfaces”, in “The Expanding World of Chemical Engineering”,
Furusake, S.; Garside, J.; Fan, L.-S. (Eds.), 2nd edition, Taylor and Francis, New York (2002)
Whitesides, G. M. “Self-Assembling Materials” Scientific American, Sept 1995, 146-149.
Gupta, V. K.; Abbott, N. L. “Design of Surfaces for Patterned Alignment of Liquid Crystals on
Planar and Curved Substrates” Science 1997, 276, 1533-1536.
Philp, D.; Stoddart, J. F. “Self-Assembly in Natural and Unnatural Systems” Angew. Chem. Int.
Ed. Engl. 1996, 35, 1154-1196.
Questions for Discussion:
1. Explain how various charges and forces at the molecular level contribute to 2-D and 3-D
self-assembly processes at the nanoscale.
2. Surfactants are key ingredients in laundry detergents. Micelles greatly increase the
amount of oily substances on fabric that can be dissolved into the wash solution. Explain
NUE: Lab-on-a-chip Nanomanufacturing in Freshman Engineering
Tomasko/Merrill/Stevenson
why a hydrophobic molecule, such as a triglyceride present in spaghetti sauce, would be
more soluble in a solution containing surfactant micelles than in pure water.
3. More than two hundred years ago, Ben Franklin demonstrated that the evaporative loss of
water from a lake could be greatly reduced by spreading a small amount of surfactant on
the surface. Fatty acids are amphiphilic molecules found in many biological systems.
When adsorbed at an air-water interface, a fatty acid molecule occupies an area of
approximately 0.20 nm2 (1 nm = 10-9 m). Calculate the volume (number of milliliters,
mL) of a fatty acid that is needed to cover the surface of a lake that has a surface area of
2000 m2. The fatty acid has a density of 0.8 g/mL and 1 g of material contains 2×1021
molecules. Why does a self-assembled monolayer of fatty acid molecules reduce the rate
of water evaporation?
4. Simple experiment to do at home: Add water to a wide pan; sprinkle a small amount of
flour onto the surface of the water; then add one drop of a water solution into which you
have dissolved some soap or detergent. What happens? Why?