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 Tue Oct 22 2013 at 5 pm, INF 267 (BioQuant), SR 44, we explained and distributed the possible subjects to the participants. Every participant received a description of his/her subject and some relevant papers. We then have met in two blocks for the talks (BioQuant seminar room Dec 6 and 7 2013 and Jan 17 and 18 2014). For physics bachelor students, participation and talk gives three credit points. This will be counted as obligatory seminar for bachelor students (PSEM) and a mark will be reported for your transcript. 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 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 should be around 30 min plus 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.

General information

Recommended books

  • Bruce Alberts et al., Molecular biology of the cell, 5th edition Garland 2008
  • 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

Subjects for talks (in brackets some research groups with papers of interest)

  1. Introduction biology (Freddy)
  2. Introduction physics (Ulrich)
  3. E Coli: chemotaxis / run and tumble / low Re swimming (Howard Berg, Tom Powers, Victor Sourjik, Stan Leibler, Harmut Loewen, Ray Goldstein)
  4. Myxococcus: bacterial gliding (Dale Kaiser, David Zusman)
  5. Trypansomes: parasite swimming (Markus Engstler, Holger Stark)
  6. Sporozoites: parasite gliding (Freddy Frischknecht, Ulrich Schwarz)
  7. Keratocytes: experiments (Theriot) / modelling (Mogilner)
  8. Dictyostelium: shape changes and actin / eukaryotic chemotaxis (LEGI) (Richard Firtel, Eduard Bodenschatz, Peter Devreotes, Herbert Levine)
  9. Integrin-based tissue cell migration: fibroblasts, cancer cells, neutrophils (Doug Lauffenburger, Claire Waterman, Misha Kozlov/Sasha Bershadsky, Michael Sixt)
  10. Migration without adhesion: blebbing etc (Eva Paluch, Erez Raz, Matthieu Piel)
  11. Collective migration, wound healing, leader cells (Pascal Silberzan, Benoit Ladoux, Xavier Trepat, Daren Gilmour, Peter Friedl)


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