Nano-synthesis Reinvented: Molecular Self Assembly

Understanding the Self-Assembly Behavior of Nanoparticles and Polymers

Recently, I’ve been diving deep into nanotechnology and a super unique component of nanotechnology is molecular self assembly. The idea of certain particles forming into different structures under different conditions really blew my mind so I decided to go a bit deeper into this, read some papers and write a review about what I’ve learned and some of my key takeaways. You may need some background on nanotechnology before being able to fully understand this…so check out my introduction to nanotechnology article here!

Molecular Self Assembly

Molecular self assembly has been commonly found in nautre and has very recently, emerged as a new approach to chemical synthesis, nanotechnology, polymer science, materials and engineering. These types of systems occur mainly at the intersection between these types of topics. Many molecular self assembling systems have been developed. Ranging from bi and tri block polymers to even complex DNA assembly systems as well as simple and complex protein and peptides. This method of self assembly is a huge advancement in the molecular engineering process and is only continuing to grow from here.


Molecular self-assembly is a type of bottom–up approach in which molecules arrange thmselves without any external guidance. Through molecular self assembly, the structure that is wanted is programmed in the shape as well as in the functional groups of the molecules. This type of approach has various advantages.

  1. It executes the most difficult steps in todays nanofabricaiton processes, including the intricate atomic level modifications through well established techniques used in synthetic chemistry.
  2. It takes shape from the many examples within biology for inspiration since self-assembly is one of the most important strategies used in biology for the development of complex, functional structures.
  3. It has the capability to incorporate biological structures directly as components in the final systems.
  4. It requires that the target structures be the most stable thermodynamically, it tends to produce structures that are relatively defect-free and self-healing.

So there are two main methods within molecular self-assembly:

The first method is to use a part of a previously formed nanostructure for the base and then coating it in free atoms of its own kind. Once immersed in these atoms, the strucutre would eventually develop irregular surfaces that would then cause it to be more likely to attracting more molecules. This then causes a morph in the structure and this pattern continues to repeat by getting more and more free atoms resulting in creating a larger component of the nanosensor.

The second method is much more complicated. It starts with a variety of complete sets of components that automatically assemble themselves into a finished sensor. This has only been done so far thorugh manufacturing microsized computer chips. If this method were to be perfected at the nanoscale, we would be able to completely disrupt the nanosensor industry and manufacture them at a quicker rate and much cheaper.

Using these sensors and the process of molecular self assembly, we are able to apply it to many segments of molecular self assembly. For example, tissue engineering, self assembly of proteins, as well as DNA Self assembly.

Molecular Self Assembly for Tissue Engineering

Currently, self assembling peptide based biomaterials are being tested and developed for use as a 3d tissue engineering scaffolds and also for drug release appllications. Chemical synthesis provides a custom made peptides in small quantities, but production approaches based upon transgenic organisms might be very cost effective when trying to scale the production.

Many studies over the past decade have been targetted to the design and use of artificial self assembling peptides for tissues engineering . There have been many advancements related to the chemical and structural properties of these tissues that are self assembled.

The peptide systems developed include a form of ‘molecular Lego’, which can form hydrogel scaffolds for tissue engineering; ‘molecular switches’, which can act as actuators, ‘molecular hooks and Velcro’ for the surface engineering, ‘molecular capsules’ for protein and even gene delivery and ‘molecluar ccavities’ for biomineralization.

Protein Self Assembly

The self-assembly of proteins into small-scale complexes plays a crucial role in biology. Under certain conditions, proteins also have the ability to self assemble into various structures that range within nanometers. This process is almost as common as complexation( the combination of individual atom groups, ions or molecules to create one large ion or molecule) and is crucial to biology.

Some proteins, such as those that make up viral capsids or the outer shell of bacterial compartments and they self-assemble by design. Others do so when something goes wrong: for example, a conformational change triggers the aggregation of amyloidβ-protein into fibrils and a single-point mutation in hemoglobin leads to its polymerization(the process of reacting monomer molecules together).

Understanding protein self-assembly is fundamental to many physiological and industrial processes. For example, the fibrillization(process of forming fibers)of Aβ is a feature of Alzheimer’s disease and the polymerization of mutant Hb is the primary cause in sickle-cell anemia; as well as many other protein bourne diseases.

DNA Molecular Self Assembly

Here the block is a honeycomb lattice of non parallel scaffold helices. Other staple strands also wind in an antiparallel direction around the scaffold strands to assemble b-form double helices that are assigned initial geometrical parameters. These crossovers between the adjacent staple helices are restricted to only the intersections between the block and every third layer of a stack of planes orthogonal to the helical axes, spaced apat at intervals of 7 base pairs, or two thirds of a turn. Crossovers between adjacent scaffold helices are permitted at positions displaced up or down of the corresponding staple-crossover points by 5 base pairs or a half-turn.

The first steps in the design process are carving away duplex segments from the block to define the target shape, and then bringing in the. scaffold crossovers at only certain allowed positions so it has to create a singular scaffold path that visits all remaining duplex segments. Next, staple crossovers are added at all permitted positions on the shape that are not 5 base pairs away from a scaffold crossover; this exception maintains the local crossover density along any helix-helix interface at roughly one per 21 base pairs. Certain components are introduced into staple helices to define the staple strands whose lengths are between 18 and 49 bases. Possesing an average between 30 and 42 bases. Occasionally, staple crossovers are removed at the edges of the different shapes to allow the adjustment of staple lengths to tailored values. Then, unpaired scaffold bases are often introduced at the ends of helices to minimize undesired multimerization or else to accomodate later addition of connecting different staple strands that meditate desired multimerization. And finally, the last step is to thread the actual scaffold sequence on the target scaffold path to determine the complimentary sequences on the staple strands.

Key Learning Points/Takeaways

So that was a lot of info that had just been thrown at you, lets just breifly sum up my key takeaways after learning about these transformative applications and papers I read about molecular self assembly:

  1. To start off, molecular self assembly is one of the most powerful and useful fabrication/synthesis techniques that should be developed further in nanotechnology in order to fully utiilze the potential of this transformative technology.
  2. Nano sensors have incredible potential in almost every industry, however, the method that we are currently using to fabricate them doesn’t make sense. Molecular self assembly solves this problem and allows us to optimize the potential of nanosensors.
  3. DNA Self Assembly allows DNA to guide self assembly for various structures or crystals and has a ton of potential with synthetic biology and synthetic chemistry applications.
  4. Understanding protein self-assembly is fundamental to many physiological and industrial processes. By understanding this and this process especially within self assembling proteins, we are able to solve some of the biggest challenges within neurodegenerative diseases.
  5. By leveraging molecular self assembly for tissue engineering, we are able to solve some of the biggest health problems all through using self assembly and re-engineering tissues in our body.
Nanotechnology, more specifically, molecular self assembly has the potential to impact billions and reshape the way we live in the next 5–10 years. The only barrier is a solid fabrication/synthesis method so that we can really leverage this technology. Molecular self assembly solves this and we will be experiencing a complete shift in many industries due to this.

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