Hess:Notebook/Biomod/2011/02/02

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Entry Author: Andrew Ghazi
Entry Subject: Test
Entry:
Here I am testing how to make entries into the notebook. Sweet. It worked.

So here are our ideas for the moment:

 1. Genetic engineering of hemoglobin
 2. Microtubule sheets for force multiplication of kinesins
 3. Electric power from ATP
 4. Smart indicator supermolecule (multi-receptor recognition by multifunctional drug delivery vehicle)
 5. Slow protein unfolding by motor proteins.
 6. Self-healing
 7. Nanofactory using molecular shuttles
 8. Circuit assembly by molecular shuttles 


Entry Author: Ely Shapiro
Entry Subject: Test
Entry:
I think i may finally understand this technology. Hope so.

Entry Author: Andrew Ghazi
Entry Subject: Test
Entry:
Ely successfully makes her first notebook entry. Congratulations.


Entry Author: Andrew Ghazi
Entry Subject: Microtubule sheets
Entry Time: 9:42 PM
Entry:
So here I'll try to expand on what I had in mind for the microtubule sheet idea. Basically I was thinking of the same "kinesin motors pushing microtubules along" idea, except a number of microtubules have been aligned parallel to each other and connected to form a raft-like structure. Hopefully, this will travel in the direction of the raft's alignment on the motors, and be able to deliver a larger force to whatever cargo is attached than a single microtubule.

When I came up with this idea, I was trying to think of a novel way to increase the largest force obtainable from the kinesin/microtubule systems that Professor Hess's lab has been working with in the past. If we manage to get this to work, we could potentially multiply the maximum obtainable force by however many microtubules we are able to form into the raft. This might help overcome the problem of flagellate bacteria attached to the microtubules being able to swim away.

Potential problems I foresee running into:

  1. Getting the microtubules parallel
    1. We may be able to use the existing directional pathways to line them up, then apply whatever we use to attach them.
  2. Attaching the microtubules
    1. This I see being one of the largest problems. Hopefully the usual biotin/streptavidin combination will work and be strong enough. I am not familiar enough with length/force scales on which this combination works to determine the feasibility of this.
  3. Kinesin motors interfering with adjacent microtubules during "operation"
    1. This will most likely depend highly on what compounds are used to attach the microtubules.
  4. Getting microtubules of relatively uniform length
    1. This entire setup/idea (if feasible in the first place) would probably still work somewhat with microtubules of variable length, but we don't want the variability too high lest the "frayed" ends start to split the raft apart as they are pulled in different directions.

Overall, unless we can find something like this that has been tried before, we're probably just going to have to get creative and try new things to get it to work.

Entry Author: Parnika Agrawal
Entry Subject: Test
Entry:
How about aligning these microtubules in the form of a cylindrical bundle instead of a raft? That may be more space-efficient. Also, what is the problem of the flagellate bacteria swimming away?

Entry Author: Andrew Ghazi
Entry Subject: Microtubule sheets
Entry Time: 11:58 PM
Entry:
I would be concerned that making a 3D structure like a cylinder (as opposed to a 2D sheet) would be unnecessarily complex. It would probably also make it much more difficult to get the kinesin motors to bind across the entire surface of the microtubule super-structure's surface. Furthermore, 2D sheets could potentially be able to deform to rounded surfaces. Could you say why you think space-efficiency might be an issue?

I recalled during the first time I heard Professor Hess talk about his research (during a lecture in BMEN 1001 Engineering in Medicine) he mentioned attaching various cargo to the microtubules to have them pulled along. In the review he sent me it only mentions nanospheres, probe DNA, and antibodies, but during the talk I remember he mentioned trying to attach flagellate bacteria. Given their relative sizes (a 1um bacterium attached to a microtubule only 25nm in diameter) the bacteria was able to just swim away. I may be misremembering the details he gave as to whether this had actually been done or if it had just been inferred. At any rate, my thinking is a 2D sheet would grant a much higher surface area to attach the bacterium to, thus making it much more difficult for the bacterium to swim away.



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