Mechanotransduction in Collective Cell Migration and its Synthetic Mimic

Speaker:     Joachim P. Spatz

Department: Cellular Biophysics at Max Planck Institute for Medical Research,                                  Biophysical Chemistry at University of Heidelberg   

Subject:       Mechanotransduction in Collective Cell Migration and its Synthetic                                Mimic

Location:    TU Delft (BN)

Date:           8-9-2017

Author: Antoine Rolland

The lecture was divided into two parts. The first part was about the dynamic movement of skin cells, which is influenced by different forces acting on them. The second part was about how this behavior could potentially be mimicked in synthetic cells.

In the first part, Joachim Spatz began by saying that group movement is a very interesting topic in biology. From birds flying together to cells moving in groups, it is very exciting to study the way they move. Joachim Spatz has been looking at the way skin cells move when there is no boundary on one side of the cells. This is comparable to the way skin cells move in the process of healing a wound. What is well known is that there are so-called leader cells that begin to move into the open space, and that a group of cells go and follow that leader cell. What was found out is that these leader cells are already determined before they go and lead the other cells. This was discovered by measuring the force that was on the cells. What was observed was that there were strong forces behind the leader cells, when that cell cannot be distinguished yet. What was also very interesting, was that a leader cell always ‘recruited’ nearly the same amount of cells. This can be explained in a mechanical way, because this is the amount of cells that a leader cell can reach with the force that it exerts.  What I found the most interesting and surprising about this part is how mostly physical properties determine the way the cells move, rather than the biological properties of the cells. Joachim Spatz explained that there are sensors in the cells that can sense the force on them, and that in this way the leader cells can be determined. Moreover, the density had a big impact on the way the cells moved into the open space. The process went a lot faster when the density was lower. A higher density required to first eject some cells into the upper layer, before the process could start properly.

In the second part, Joachim Spatz explained how this movement of the cells could potentially be mimicked in synthetic cells. For this, a stable cell environment is needed. This can be achieved by creating nanodroplets with a polymer outside layer. To make an equivalent of the cell membrane, a lipid bilayer was added that bound to this polymer. It was proven that by adding components to this nanodroplet one after another, the result was better than when adding pre-assembled components. These nanodroplets also showed forms of adhesion, making it possible to apply and let them exert forces to potentially make the system from the first part in a synthetic manner. After the talk, we discussed some things with Joachim Spatz. What was interesting was the following question that arose: what exactly is life? To Joachim Spatz, for his cells to really become artificial life, they should be able to replicate, to move by their own and to create energy for themselves from the environment.

Leader cell with its follower cells

What really stood out to me from this talk is that physics and forces inside cells are way more important than I thought. Also, analyzing group movements of different kind of cells, could be very interesting for future research. Maybe we would discover that in group movement forces are often a very important factor. For me, this group movement is very interesting, and I wouldn’t mind learning more about this. Also, I think we are very close to creating synthetic life. Of course, ethical questions will rise if eventually real synthetic life could be created. I think this will be a big challenge for the future.

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Quo Vadis: Cees Dekker

Speaker: Cees Dekker
Department: Bionanoscience, TU Delft
Location: TU Delft
Date: July 6, 2017
Author: Teun Huijben

As start of the summer Quo Vadis of the Bionanoscience Department, Cees Dekker was invited to give a talk. Literally translated from Latin, Quo Vadis means: ’Where are you going?’. In light of this title Cees decided to give a summarizing talk about covering all the exciting research happening in his lab and what he hopes to achieve in the next years.

Since Cees has the largest lab of the department, of lot of different topics are studied in his group. The different topics can be roughly divided into three categories: developing novel nanotechnologies, studies on chromosomal organization and developing the synthetic cell. Of each of these subject he highlights some interesting ongoing studies and his vision on the future.

The first topic Cees elaborates on are the novel nanotechnological techniques his group is developing. The most important technique is the solid state nanopore, which is a very small hole in a thin membrane. When a voltage is applied over the chip, an ionic current starts running and DNA can be dragged through the pore, because of its overall negative charge. While translocating the pore, the DNA blocks the ionic current partly and the decrease in current can be measured. The nanopore technique can be used in different studies. Firstly, it may enable sequencing of DNA optically, when the pore is used in combination with plasmonic structures. The gold plasmonic structures create a high-energetic field trapping the DNA in the pore. In combination with Raman spectroscopy, chemical structures of the DNA can be deduced from the emitted radiation.

Secondly, nanopores are also useful in studying nuclear pore complexes. By covering the inside of the pore with nuclear pore proteins, the transport of proteins can be mimicked through this artificial pore. The advantage is that it can be done in vitro, instead of in living cells. At last, they are also trying to sequence proteins using biological nanopores.

The second main part of Cees’ talk was about the study of chromosome organization. For multiple years, his group is interested in the higher structures of DNA and how that structure is determined. An important part of chromosome structures are supercoils, in which DNA is coiled up to store it in a compact way and suppress transcription. The main question is whether these supercoils (or plectonemes) are sequence dependent. His group developed a new technique to study the coiling, and indeed the position of the supercoils is dependent on the sequence of the DNA. Modeling of the DNA gave the insight that certain sequences have an intrinsic curvature, and the model predicted which sequence will increase the probability of having a supercoil, since the tip of the supercoils needs Experiments with these sequence indeed showed a higher probability of having a supercoil at that position. This shows that the intrinsic curvature of the DNA determines higher structures of the chromatin, so the DNA sequence not only codes for proteins, but also for its own structure.

The last part of his talk was about making a synthetic cell, the ultimate dream of Cees. The goal is to create a vesicle (liposome) with a working division mechanism inside. One idea is to use the bacterial MinE-MinD oscillating proteins to position a FtsZ-ring in the middle of the cell and actively contract this ring to divide the cell. This idea will need some years to become reality, so right now his group is studying the different components of this idea separately and hopefully the first ’synthetic’ cell will be there is a few years.

What I found particularly nice about this talk was that Cees summarized all the research that is currently done in his large lab. In this way the department got a better idea of all the things happening within this part of Bionanoscience. Besides that, Cees is a very enthusiastic speaker what makes if nice to listen to.