Ruprecht Karls Universität Heidelberg

Seminar Molecular Biology and Biophysics of Cell Motility

This interdisciplinary seminar addresses students after the 4th semester from physics, biology, molecular biotechnology and related fields. It is jointly organized by Friedrich Frischknecht (biology, parasitology) and Ulrich Schwarz (theoretical biophysics). In our Vorbesprechung on Wednesday Oct 19 at 4pm, INF 267 (BioQuant), SR 44, we will fix the dates and distribute the subjects.

Every participant will receive a description of his/her subject and some relevant papers. We then will meet in two blocks for the talks, each taken place on one Friday afternoon and one Saturday morning. For physics bachelor students, participation and talk gives two credit points. This will be counted as obligatory seminar for bachelor students (PSEM) and a mark will be reported for your transcript. For physics master students, you can get six credit points for an obligatory master seminar (MVSem), but for this you also have to hand in a 15-20 pages written paper on your subject after the seminar is finished. For biology students, the details are more complicated and have to be worked out with the Studiensekretariat. Everybody is welcome to ask questions to the organizers when preparing the presentation. Active participation during discussions is expected. In the following we describe the general scientific idea of this seminar.

The ability to move is one of the most fundamental features of biological cells and nearly as important as their ability to grow and divide. A notable exception from this observation is the case of plant cells. However, most other cell types, including bacteria, unicellular eukaryotes and animal cells, usually require some kind of motility in order to function properly. Understanding how cells move is not only interesting from an academic point of view, it is also a subject of large practical relevance, ranging from the design of artificial motility in materials science to medical applications like the control of malaria infection or cancer metastasis. In this seminar, we will introduce the fundamental biological and physical mechanisms underlying cell motility, and discuss state-of-the-art research in this interdisciplinary research field.

As a starting point, we first note that there are certain physical limitations that restrict the way cells can move. The most important observation in this context is that cells have a typical size of 50 um (exceptions confirm the rule). One simple explanation for this finding could be that the diffusion constant of proteins is essentially determined by the Stokes-Einstein relation to be around (10 um)^2/s. Therefore cells with a size strongly exceeding 10 um would not be able to transfer intracellular signal on the typical time scale of extracellular changes (seconds).

Water is the basis of all life as we know it. Cells are not only made up of aqueous medium inside, they also are surrounded by aqueous medium. With a typical cell size of 50 um and a typical velocity of um/s, it follows immediately that cell move in the low Reynolds number regime. This means that their movement is very different from our daily life experience of using inertia to move. Instead, microorganisms move as a human would if being immersed in a swimming pool filled with honey. One important aspect of the seminar will be to learn about the specific consequences of this situation.

On the molecular biology side, we can roughly differ between the motor driving the cell and the decision-making circuits regulating this motor. For bacteria and unicellular eukaryotes, the cell body is usually relatively rigid and locomotion is achieved by the movement of flagella and cilia. For animal cell, shape changes are key and are mainly effected by the actin cytoskeleton. In both cases, there is upstream regulation that picks up information from the environment by receptors and processes this information in a signaling network. Regulation of cell motility can be as complex as cell cycle control or fate decisions, and is tightly integrated with the structural features of cells, including the biology and physics of membranes and the cytoskeleton.

Despite the fundamental limitations arising from the underlying physical and biological principles, life has found many ways that allow cells to move. In order to understand which kinds of systems we will deal with in the seminar, it is instructive to consider the following criteria for classification:

  • Active versus passive: eg white versus red blood cells
  • Shape: movement with or without cell shape changes
  • Contact: movement in solution (swimming, flowing with the stream) or in contact with surfaces (gliding, crawling)
  • Molecules: movement based on the actin cytoskeleton (eg lamellipodia for animal cells or conveyer belt for sporozoites), other cytoskeletal proteins (eg sperm protein for nematodes), membranes (eg movement by blebbing), etc.
In each of these cases, mathematical models have been developed to achieve a quantitative understanding.

As a student, you can pick either a biology subject describing the molecular basis of a given system, or a physics subject explaining quantitative experiments or mathematical modelling. Ideally, we would like to have a pair of one biology and one physics talk for each subject. Each talk of a single participant should be around 30 min plus up to 15 min discussion. Because the literature is mainly in English, we recommend to give the talk in this language. Suggestions for additional subjects are most welcome.

Recommended reading

  • Introduction to special issue on motorisation of pathogens, editors Jake Baum and Freddy Frischknecht, Seminars in Cell and Developmental Biology 2015
  • Physical constraints for pathogen movement, Ulrich Schwarz, from this special issue
  • Bruce Alberts et al., Molecular biology of the cell, 6th edition Garland 2014
  • Dennis Bray, Cell movements: from molecules to motility, 2nd edition Garland 2000
  • Peter Lenz, editor, Cell motility, Springer 2007
  • Howard Berg, Random walks in biology, Princeton University Press 1993
  • Rob Philipps, Jane Kondev and Julie Theriot, Physical biology of the cell, 2nd edition, Taylor and Francis 2012
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