Hess:Continuous Notebook

'''Entry Author: Andrew Ghazi  Entry Subject: Continuous Notebook test  Entry Time: 05:00 PM 2/12/2011  Entry: ''' Testing to see if I got this continuous notebok page set up properly. Seems to be working. Let me know if any changes should be made.

'''Entry Author: Ely Shapiro  Entry Subject: Continuous Notebook test/Ely makes her first attempt at technology  Entry Time: 08:00 PM 2/17/2011  Entry: ''' Here's a somewhat brief synopsis I have of self healing. Hopefully you find this of interest and use. I'm working on the energy harvesting from ATP right now, so that will be posted later. Enjoy!

The field of self healing has recently come into popularity in scientific research. There have been a few models for the mechanism, which papers have written about—some of them work, and some of them don’t. Our goal would be to either find a new mechanism or attempt to validate an unproven model. The latter would make more sense in our work for this summer. The topic is as it sounds—self healing, a material healing itself. Biological materials such as skin and bone exhibit self healing mechanisms, and would hopefully provide insight to research for self healing for man made systems. The Toohey (2007) article covers a mechanism in which the material of the original structure is loaded into the surface, so that when it cracks, the regions containing the healing material will fill in the crack. The problem with this model is that there is only one supply of the healing material. There is no current method to re-supply the material, so there could be some potential discoveries there. However, I ‘m not sure if our current knowledge, or the span of our time to research will make this a feasible option. We will probably prefer to go with the method suggested by Henry’s paper, which consists of creating molecular shuttle systems in which loaded microtubules travel along kinesin and deposit the material where damage has been done to the surface. This has been suggested, but as far as I am aware, the method hasn’t been confirmed to work. This seems like a good option for us to look into, especially because it is such a multifaceted project. The specifics we would have to look into would include (1) loading the microtubules (2) ensuring that the kinesin sticks to the gold surface (3) ensuring that the microtubules follow the path set forth by the kinesin (4) instigating a release of the cargo onto the damaged site. I don’t know if this is relevant, but I did some work this year on that project, but instead of using molecular shuttles, I eliminated them in place of the bonds that can be created by proteins. In essence, the glass slide, covered in gold, was coated in a protein, and gold nanopartices were covered with BSA (a fluorescent protein). Ideally, the coated gold nanoparticles would stick to a damaged site on the surface by a chemical attraction. This hasn’t been proven yet, but would probably be too simple for all of us to work on, but it would be an interesting side thought. One (random and outlandish) idea that I came up with recently (I often come up with strange things, feel free to keep me in check) involves using Self Assembled Monolayers (SAM) to attract different proteins. That’s just because I think SAMs are really cool. It could be used for patterned deposition. I don’t know how useful that is, though, but it sounds interesting, to me at least. This is an interesting article http://pubs.acs.org/doi/full/10.1021/cr9502357 If you feel like doing any additional reading in your spare time (as if you haven’t had enough already). This project will take a fair amount of work, but the idea is very interesting (or at least I think so), and the applications would be phenomenal in real life technology.

'''Entry Author: Ely Shapiro  Entry Subject: A meager proposal  Entry Time: 08:50 PM 2/17/2011  Entry: ''' ATP FOR ENERGY (it would be nice, but I’m skeptical)

The electric eel (Electrophorus electricus) can generate potentials around 600 V to stun prey and ward of predators. (link to the article that I found this in: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2767210/pdf/nihms128884.pdf )The ion concentration gradient model that they use creates this energy. Our goal would be to design an artificial cell to capture the energy that they create. The Sundaresan (2010) article suggested a novel method of capturing the energy, but it yielded a low energy output of about 40 mV. It would be interesting to work off the model of the electric eel’s method of creating this energy, and then capturing it. This, interestingly, uses what is found in nature and tries to convert it to a man made mechanism. I don’t know as much about this procedure as I do the self healing (hence why this write up is much shorter), but the article is pretty comprehensive and not too complicated, so I recommend reading it. We would essentially set up one inverted membrane near one noninverted membrane. The membranes were equipped with different pumps and channels, and the electric charge gradient created energy. I don’t think this is the best option for our research this summer, we would have to follow in the tracks of previous research, and I don’t think that it aligns with the current research that our lab does. The procedure is difficult for a pretty low energy output. If you have any ideas about how we should use this idea, let me know, I may be missing a part of the concept.

'''Entry Author: Andrew Ghazi  Entry Subject: Continuous Notebook test  Entry Time: 11:19 PM 2/21/2011  Entry: '''

Molecular Circuit Assembly: What, How, and Why

What: Ideally we would be creating an electrical connection through the use of microtubule shuttles. A nanowire (actin coated in metal nanoparticles) would be picked up, carried along by the shuttles, and then deposited between two electrodes, creating the connection.

How: We would likely need to use a shuttle path guided by surface topography and chemistry going between the two electrodes such that as the cargo-laden shuttle passes, the nanowire binds to the electrodes. This would obviously be easiest if the nanowire’s length was perpendicular to that of the shuttle, but given that the nanowires in the Patolsky paper were roughly 3μm long, holding something that long with only a few connections to the shuttle on the middle probably wouldn’t work. Thus, we’d need to find a way to have the nanowire attach as it passed parallel to the electrodes.

If the deposition of the nanowire depends on proteins to remove the nanowire from the shuttle and bind it to the electrodes, these same proteins may prevent an electrical connection. In that case, the entire system would need to be heated to the point of combusting the proteins, leaving only the electrodes and nanowire intact. However, then the connection between the electrodes and the nanowire would likely be very weak, potentially necessitating that we not move the entire assembly for it to function. In that case, it begs the question if making such a connection in the first place was worth it at all if it was going to end up being so weak.

Alternatively, if we are able to coat only the top surface of the actin molecule in the metal nanowires, it might be possible to have the nanowire itself act as the shuttle, cutting out the microtubule middle man.

It also occurred to me that the charge difference induced into the ends of the nanowire by the potential difference from the nearby electrodes could provide some attractive force between the wire and the electrodes. I'm not familiar enough with the materials science to know whether this will be noticeable or negligible at this scale, but it's worth thinking about if the voltage difference between the electrodes can be scaled to a range where this effect comes into play. Of course, it would also disappear entirely once the connection was made, so there would still need to be some sort of adhesive holding the two together.

Why: Electronic circuits get smaller and faster every year, and this could be the start of some extremely small and extremely fast circuits. That said, I think given the inherent messiness of biological systems, a plan like this would have to be extremely refined to work even moderately well.

'''Entry Author: Parnika Agrawal  Entry Subject: Smart Indicator supermolecule  Entry: ''' Smart Indicator Supermolecule (Nanovector)

What: We aim to create a molecule/device capable of imaging and drug delivery to the targeted cells of the body. This molecule would also work as a dynamic sensor, so that we can get real-time data for the path that it follows, from the time it was introduced in the body till the time it is swallowed by the cell-membrane. To make it target-specific, we make use of polyvalency concepts as detailed in the Joshi’s polyvalency paper.

Why: This will revolutionise the way medicine is practiced currently, and will help in early diagnosis and way more effective treatment of diseases like cancer. Applications of this device also lie in gene delivery and preventive medicine.

How: Several types of molecules have been used for this purpose by different researchers, some of them are CNTs, dendrimers, fullerenes, nano-cantilevers, superparamagnetic metal nanoparticles and metal nanoshells.

From the attached paper:

The opportunities for nanovector therapeutics depend on the successful addressing of the three critical challenges: first, the development of multimodal localization capabilities, that exploit multiple, concurrent mechanisms to obtain preferential concentrations of the therapeutic action at the intended lesion sites; second, the integration in nanovectors of multiple methods for the sequential overcoming of the natural defenses that create barriers against the reaching of the intended lesions, regardless of their intrinsic targeting abilities; and third, the ability of comprising multiple therapeutic agents within nanovectors, to attain their synergistic co-delivery at lesion sites.

Significant progress has been reported in the literature toward addressing the first two of these challenges, but attention to the development of a system that incorporates all of the desired functions has been minimal

What has not been done in this, and what we could try doing:

1.Use molecular motors for active transport of the nanovector across the cell membrane.

2.Creation of multiple-stage and multiple payload-delivery systems.

I would recommend you to glance through the paper(s) attached to get a better idea of the concept.

http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6VRX-4GFCR5M-1&_user=489944&_coverDate=08%2F31%2F2005&_rdoc=1&_fmt=high&_orig=gateway&_origin=gateway&_sort=d&_docanchor=&view=c&_searchStrId=1656996011&_rerunOrigin=scholar.google&_acct=C000023778&_version=1&_urlVersion=0&_userid=489944&md5=99e4b05c076c6ba57ba57ccc25ccab3e&searchtype=a

http://web.mit.edu/kym/OldFiles/Public/paper/cancer_nanotechnology.pdf

'''Entry Author: Parnika Agrawal  Entry Subject: Nanofactory using molecular shuttles  Entry: '''

For this project idea, I found an entire website dedicated to molecular assembly. This gives a good idea of the current progress and the future challenges.

http://www.molecularassembler.com/Nanofactory/index.htm

'''Entry Author: Andrew Ghazi  Entry Subject: Force multiplication by microtubule sheets  Entry Time: 1:17 PM 2/27/2011  Entry: '''

What: We would create a raft-like structure of microtubule sheets aligned parallel to one another and bound together. Hopefully, then net force that can be applied to such a structure when held in place on a kinesin coated plate is proportional to the number of microtubules in the sheet, and much larger than that of a single microtubule.

Why: This could present a new step along the path to generating macroscopic scale forces from a bottom-up approach.

How: See my posts on the first day of the original notebook.

'''Entry Author: Andrew Ghazi  Entry Subject: Microtubule raft binding and shaping  Entry Time: 10:00 PM 3/7/2011  Entry: ''' I've been thinking about how we will need to align the microtubules in order to bind them into the raft shape. My first thought is to have biotinylated microtubules travel along a unidirectional path (made unidirectional with the arrowhead rectifiers), then run into a removable wall, where they hopefully stop, then bind together. Remove the wall, the raft moves.


 * 1) We would need to have the path be fairly narrow to prevent the tubules from just tangling up at the wall and/or changing direction significantly before they hit the wall and/or changing direction as they are pushing against the wall.
 * 2) Hopefully running this with a fairly low concentration of ATP powering the kinesin motors would discourage the formation of microspools.
 * 3) Designing a wall that is removable might be difficult. As I understand it the usual pathways are molded out of polyurethane, so we'd have to find another way of creating a wall such that we can remove it after the microtubules formation.

I've got some other ideas on how to get the microtubules to connect, but right now, even though this idea seems kind of iffy, this is the best I have.

I'm also slightly worried about the variability of length of the microtubules in the raft. If it varies too much, the free ends from the longer microtubules could swing around from Brownian motion then head off in another direction from the rest of the raft, splitting the entire structure. Hopefully the variance of microtubule stock is low, and if it isn't we will need to figure out a way separating off microtubules of a specific length. My initial idea on how to do that if possible is as follows: after the microtubules have hit the wall, we irradiate the back ends of the microtubules like so with UV. Since we know the forward ends are lined up at the wall, the free ends all get cut to the same length, and hopefully the raft ends up as a nice square shape. My worry there is of course that the raft would then disintegrate as we lose the cap on the end of the microtubule and the tubulin subunits disintegrate off.

'''Entry Author: Andrew Ghazi  Entry Subject: Force comparisons  Entry Time: 9:00 AM 4/18/2011  Entry: '''

In the Linke paper Professor Hess provided, figure 6 shows one myofibril made of 18 sarcomeres with an average width of 1.1micrometers (approximately circular) produces about 150mN/mm^2. This works out to 7.9 pN/sarcomere, which means that one sarcomere produces a force roughly equivalent to that produced by one kinesin protein.

'''Entry Author: Andrew Ghazi  Entry Subject: Goal statement  Entry Time: 5:11 PM 5/3/2011  Entry: '''

The goal of the project is to build a structure that can selectively transport nano and micro-scale particles for distances no less than 1mm at no less than 200nm/s (these dimensions are the lower bounds of what we should aim for). The biological "train" would effectively move cargo efficiently and with less loss of cargo than the existing method of transport along microtubules.