Speaker: Joachim P. Spatz
Department: Max Planck Institute for Medical Research, department of Biophysical Chemistry, Heidelberg, Germany
Subject: Sequential bottom-up assembly of synthetic cells
Location: TU Delft, BN-seminar
Author: Maricke Angenent
Joachim Spatz was the invited speaker of today’s seminar. He presented a talk which was organized in two main topics, starting with an introductory part on the self-organization of biological systems. This organization is also observed on cellular level and by making simulations of this process, the physical laws of collective cell migration can be studied in more detail. Subsequently, Spatz moved on to his most recent subject of research, which involves the field of synthetic biology. He elaborated on the progress his department has made on the creation of a synthetic cell and how this cell could be brought into a biological environment.
Collective cell migration
When comparing different forms of collective movement, whether it be on a macro or micro scale, you will find similarities no matter what the object is. One of those is that each system will find hierarchy at some point in the process. Since the similarities in collective migration were so striking, it was nothing but logical to set out for overlapping ‘rules’ involved in the behavior. This is what lead Spatz to his conducted experiments, which were mostly focused on the upper layer of skin, the epidermis. When you look from the top you can clearly see the dynamics of individual skin cells and how they are all mechanically interconnected. Consequently simulations allow for in depth analysis of how the movement is actually established. With special measurement techniques, forces on the various cells were measured, which were then used to calculate stresses between individual cells. The result obtained was that the force correlation length corresponds to the length of approximately 10 cells, meaning that the force exerted by one cell can influence the migration of other cells separated by maximally 9 others.
Fig 1. The forces involved in collective cell migration can be compared to rope pulling. The force is constantly passed to the adjacent cell, up to 10 cells further
The next experiment involved a confinement of cells. During the assay the cells were (at time t=0 ) allowed to spread to an area without any other cells. Interestingly, the result showed that even though cells are genetically identical, they do not move in the same direction nor at the similar speed. Now by combining the knowledge of before and by again computing the forces present, a so-called leader cell could be identified. A cell which is the first to move from the confined space and seemingly ‘pulls’ the other cells with him. Subsequently it was studied what the requirements were to become such a leader. To do so, the field looked at leader cells which had already appeared and then went back in time to study the prior forces and their particular location.
What I found surprising is that the system of cells always regulates back to the essential spacious organization with respect to the leader cells, even after being disrupted. Showing that it is indeed a very mechanically regulated system, including cells that collectively integrate forces together.
The synthetic cell
Overall I thought this part of the lecture was more difficult to understand than the first part, mostly because of quite some difficult terminology which I am not very familiar with, yet. Despite that it was very interesting to listen to, as it appeared to me as a promising approach to making an actual fully function cell. The main idea was that Spatz and his research group are now making synthetic cells by first stabilizing water droplets and then sequentially adding various essential cell compartments. To do so the water particle, which is a mechanically very strong template, is brought into an electric field causing the cell membrane to become more porous. Subsequently, pico-injection was utilized to inject quantified volumes into the ‘synthetic cell’. What I picked up as most important message was that the sequential addition was of real importance for it allows to reach complexities which you could not reach if you try to make the entire cell in one go.
On a personal note, I thought the seminar was very fascinating and I learned a lot of new information. I was not acquainted with all the theories behind collective cell migration, and to be honest had never acknowledged it before. However it turns out to be a very regulated process with many physical laws to be discovered. For me the second part about making a synthetic cell was what really sparked my interest. I found it amazing to find out that the basic molecule they are using to make a synthetic cell is just an ordinary water molecule! I look forward to hearing more about this kind of recent innovations in the biological field and all of the possible applications.