View source for System complexity scaling with self-assembly


As of time of writing (late 2024) we may still be far from having hit the ultimate limits of [[self-assembly]]. Even with the constraints of remaining fro the most part fully in the realm of [[topological atomic precision]]. I.e. not veering out into the realm of [[synthetic biology]] aiming to carbon copy the workings of molecular biology with heavy use of vesicles and membranes.

Note: The wording "scaling of system complexity" is chosen intentionally here as <br>
just "scaling" could be easily mistaken with size and a mere scaling in size may be <br> 
much less relevant for quantifying progress than system complexity. <br>
For details on that see page: [[Quantifying progress by scaling in achievable complexity]] <br>

== The example of 3D [[structural DNA nanotechnology]] (3D-SDN) ==

3D [[structural DNA nanotechnology]] already managed to scale complexity by a fair bit. <br>
Perhaps a good part of the way to the scale of a [[foldamer printer]]. <br>
Well, 3D-SDN is clearly not stiff enough though for [[positional atomic precision]]. <br>
It's stiffness could perhaps suffice for things like (as of 2024 not yet experimentally shown) [[Tether assisted assembly]] <br>
which can accommodate for quite large structural deformations. <br>
[[Tether assisted assembly]] would be an in-between between positional-assembly and self assembly that <br>
has not yet been experimentally explored as of time of writing (2024). <br>

3D [[structural DNA nanotechnology]] has been scaled up to gigadalton scale (hundret thousand atoms) and almost micron scale. <br>
See <ref name="Wagenbauer2017"/> (not an open access paper unfortunately). <br>
Granted that this lacks in [[termination control]] to the here in this wiki used definition of it <br>
where full unbroken spherical symmetry is considered a generalized form of non-termination. <br>
But there is other experimental work showing more [[termination control]] <br>
at the same [[hierarchical same assembly level]] and only slightly smaller size scale. <br>
See: <ref name="Zhou2022"/> (also not an open access paper unfortunately). <br>

== Known limits / challenges ==

* exponential slowdown due to part depletion thin-out
* slower diffusion speeds of larger parts

== Tricks & workaround methods ==

=== [[Hierarchical selfassembly]] === 

Already experimentally demonstrated <br>
as mentioned in the preceding 3D-SDN section.

=== [[Iterative self-assembly]] & [[Multi pot self-assembly]] ===

These may be especially helpful when making orthogonal sets of binding interfaces is hard(er). 
As e.g. with de-novo proteins vs 3D-SDN. Orthogonal set meaning both high (re)activity and high specificity.
Matching faced binding strongly mismatching faces binding weakly. Prominent binding matrix diagonal.

=== [[Circumsembly]] ===

Removing a factor of exponential drop-off in yield by providing parallel redundant pathways.
3D-SDN already does this. Internal missing pieces can be irrelevant in many cases. Related page: [[Steric trap]]. 

=== [[Squigglesembly]] ===

For building 2D structures with mere 1D assembly capabilities. <br>
Note that this is possibly not yet experimentally investigated as of tome of writing (2024). <br>
It should be combinable with other techniques for higher dimensionality (3D). <br>
Again a technique that may be especially helpful when making orthogonal sets of binding interfaces is hard(er). <br>
As with de-novo proteins. <br>

=== [[nŃon-thermal self-assembly]] ===

At scales that no longer support fast enough diffusion transport <br>
there is still [[non-thermal self-assembly]] left as an option (with some constraints).

=== Increase of effective concentration ===

In some cases 3D-SDN does this by providing a long scaffolding/templating/seed strand. <br>
Similar strategies might be possible with de-novo proteins eventually. <br>
The scaffolding strand method is specific to SDN. <br>

=== Advanced nucleation control ===

Some few nucleation seeds can be intentionally brought in <br>
in order to to knock down an intentionally too high collaborative nucleation barrier. <br>
This way one gets a few fully completed assemblies rather than many partially completed assemblies when the <br>
fee-stock is nigh depleted. <br>

=== Weak pre-bonding based misassembly self correction ===

In SDN wrongly self-assembled sites can come apart again by iterative zipping. <br>
Coorect assemblies get stabilized by collaborative bonding then there-after. <br>
Flexibility of the self-assembled chains is critical for these sort of processes. <br>
Unfortunately this is direct opposition to the goal of eventually getting to structures of higher stiffness. <br>

Note that this this is (can be?) a critical prerequisite for [[algorithmic self assembly]]. <br>

=== Algorithmic selfassembly ===

In principle this can give termination control over much larger size scales. <br>
It is no longer full "random access" termination control though. <br>
Also the technique is generally more challenging. <br>
As of time of writing (late 2024) the author is unaware of <br>
exprimental work on [[algorithmic selfassembly]] in the space of de-novo proteins. <br>

== DNA vs protein vs other ==

Some stuff that only works with DNA (or similar). <br>
Some stuff is more for proteins. <br>
{{wikitodo|Maybe make this clearer somehow by some repeated analysis pattern.}} <br>

== Related ==

* [[Hierarchical selfassembly]]
* [[Iterative self-assembly]] & [[Multi pot self-assembly]]
* [[Circumsembly]] ([[SDN]] ready does this, internal missing pieces can be irrelevant in many cases)
* [[Squigglesembly]] (possibly not experimentally investigated as of 2024)
----
* [[Non-thermal self-assembly]]
----
* [[Tether assisted assembly]] mining in some [[positional assembly]] into [[self-assembly]]

== External links ==

=== Papers ===

<references>
<ref name="Wagenbauer2017">Wagenbauer, K. F., Sigl, C., & Dietz, H. (2017). Gigadalton-scale shape-programmable DNA assemblies. Nature, 552(7683), 78–83. doi:10.1038/nature24651</ref>
<ref name="Zhou2022">Zhou, Yihao & Dong, Jinyi & Zhou, Chao & Wang, Qiangbin. (2022). Finite Assembly of Three‐Dimensional DNA Hierarchical Nanoarchitectures through Orthogonal and Directional Bonding. Angewandte Chemie International Edition. 61. 10.1002/anie.202116416.</ref>
</references>