Biophysics of Cell Motility

Many eukaryotic cells carry cilia or flagella. These whip-like cell appendages are characterized by highly-conserved cytoskeletal elements consisting of a regular arrangement of microtubule doublets. In many cells, the regular flagellar bending is powered by molecular motors that propel the cell. It is well established that Ca2+ is key for the control of bending in many cell types from sperm to algae.

Sperm are bio-machines that steer their swimming path along “chemical signposts” or chemoattractants, a process termed chemotaxis. The binding of chemoattractant to receptors on the flagellum triggers a signaling cascade that eventually leads to a change in Ca2+. Simultaneously, a corresponding change in the flagellar bending arises resulting in a chemotactic steering response. Previous research identified Ca2+ as a key player for flagellar motility. In particular, the concept was that flagellar bending is directly controlled by the absolute Ca2+ concentration. Studying intact sea urchin sperm surprisingly, we discovered that sperm navigation is not controlled by the absolute intracellular Ca2+ concentration but, instead is highly correlated with temporal changes in Ca2+, (d[Ca2+]i/dt). This provides evidence for an adaptive mechanism of flagellar motility control.

Many key questions on the understanding of cell motility and chemotaxis remain unanswered and are the focus of our current research: How do sperm decode the spatio-temporal pattern of chemoattractants and translate this information into motion? What are the physical limits of chemosensation in sperm? How do sperm cells swim in three dimensions?


Gadadhar, S., Alvarez Viar, G., Hansen, J.N., Gong, A., Kostarev, A., Ialy-Radio, C., Leboucher, S., Whitfield, M., Ziyyat, A., Toure, A., et al. (2021). Tubulin glycylation controls axonemal dynein activity, flagellar beat, and male fertility. Science 371, eabd4914. Link to MPG publication repository PuRe

Trötschel, C., Hamzeh, H., Alvarez, L., Pascal, R., Lavryk, F., Bönigk, W., Körschen, H.G., Müller, A., Poetsch, A., Rennhack, A., Gui, L., Nicastro, D., Strünker, T., Seifert, R., and Kaupp, U. B. (2019). Absolute proteomic quantification reveals design principles of sperm flagellar chemosensation. EMBO J, e102723.

Gong, A., Rode, S., Kaupp, U.B., Gompper, G., Elgeti, J., Friedrich, B.M., and Alvarez, L. (2020). The steering gaits of sperm. Philos Trans R Soc Lond B Biol Sci 375, 20190149.

Hamzeh, H., Alvarez, L., Strünker, T., Kierzek, M., Brenker, C., Deal, P.E., Miller, E.W., Seifert, R., and Kaupp, U.B. (2019). Kinetic and photonic techniques to study chemotactic signaling in sea urchin sperm. Methods Cell Biol 151, 487–517.

Saggiorato, G., Alvarez, L., Jikeli, J., Kaupp, U.B., Gompper, G. and Elgeti, J. (2017). Human sperm steer with second harmonics of the flagellar beat. Nat Commun 8, 1405.

Alvarez, L. (2017). The tailored sperm cell. J Plant Res 130, 455-464.

Kaupp, U.B. & Alvarez, L. (2016). Sperm as microswimmers - navigation and sensing at the physical limit. Eur Phys J Spec Top 225, 2119-2139.

Björkgren, I., Alvarez, L., Blank, N., Balbach, M., Turunen, H., Laajala, T.D., Toivanen, J., Krutskikh, A., Wahlberg, N., Huhtaniemi, I., Poutanen, M., Wachten, D., and Sipilä, P. (2016). Targeted inactivation of the mouse epididymal beta-defensin 41 alters sperm flagellar beat pattern and zona pellucida binding. Mol Cell Endocrinol 427, 143-154.

Mukherjee, S., Jansen, V., Jikeli, J.F., Hamzeh, H., Alvarez, L., Dombrowski, M., Balbach, M., Strünker, T., Seifert, R., and Kaupp, U.B. (2016). A novel biosensor to study cAMP dynamics in cilia and flagella. eLife 5, e14052.

Fechner, S., Alvarez, L., Bönigk, W., Müller, A., Berger, T., Pascal, R., Trötschel, C., Poetsch, A., Stölting, G., Siegfried, K.R., Seifert, R., and Kaupp, U.B. (2015). A K+-selective CNG channel orchestrates Ca2+ signalling in zebrafish sperm. eLife, e07624.

Jikeli, J., Alvarez, L., Friedrich, B.M., Wilson, L.G., Pascal, R., Colin, R., Pichlo, M., Rennhack, A., Brenker, C., and Kaupp, U.B. (2015). Sperm navigation along helical paths in 3D chemoattractant landscapes. Nat Commun 6, 7985.

Strünker, T., Alvarez, L., and Kaupp, U.B. (2015). At the physical limit — chemosensation in sperm. Curr Opin Neurobiol 34, 110-116.

Jansen, V., Alvarez, L., Balbach, M., Strünker, T., Hegemann, P., Kaupp, U.B., and Wachten, D. (2015). Controlling fertilization and cAMP signaling in sperm by optogenetics eLife 4, e05161.

Seifert, R., Flick, M., Bönigk, W., Alvarez, L., Trötschel, C., Poetsch, A., Müller, A., Goodwin, N., Pelzer, P., Kashikar, N.D., Kremmer, E., Jikeli, J., Timmermann, B., Kuhl, H., Fridman, D., Windler, F., Kaupp, U.B., and Strünker, T. (2015). The CatSper channel controls chemosensation in sea urchin sperm. EMBO J 34, 379-392.

Schiffer, C., Müller, A., Egeberg, D.L., Alvarez, L., Brenker, C., Rehfeld, A., Frederiksen, H., Wäschle, B., Kaupp, U.B., Balbach, M., Wachten, D., Skakkebaek, N.E., Almstrup, K., and Strünker, T. (2014). Direct action of endocrine disrupting chemicals on human sperm. EMBO Rep, e201438869.

Alvarez, L., Friedrich, B.M., Gompper, G., and Kaupp, U.B. (2014). The computational sperm cell. Trends Cell Biol 24, 198-207.

Krähling, M., Alvarez, L., Debowski, K., Van, Q., Gunkel, M., Irsen, S., Al-Amoudi, A., Strünker, T., Kremmer, E., Krause, E., Voigt, I., Wörtge, S., Waisman, A., Weyand, I., Seifert, R., Kaupp, U.B., and Wachten, D. (2013). CRIS- a novel cAMP-binding protein controlling spermiogenesis and the development of flagellar bending. PLoS Genetics, e1003960.

Hirohashi, N., Alvarez, L., Shiba, K., Fujiwara, E., Iwata, Y., Mohri, T., Inaba, K., Chiba, K., Ochi, H., Supuran, C. T., Kotzur, N., Kakiuchi, Y., Kaupp, U.B., and Baba, S.A. (2013). Sperm from Sneaker Male Squids Exhibit Chemotactic Swarming to CO2. Curr. Biol. 23, 775-781.

Kashikar, N. D., Alvarez, L., Seifert, R., Gregor, I., Jäckle, O., Beyermann, M., Krause, E., and Kaupp, U.B. (2012). Temporal sampling, resetting, and adaptation orchestrate gradient sensing in sperm. J. Cell Biol 198, 1075-1091..

Alvarez, L., Dai, L., Friedrich, B. M., Kashikar, N., Gregor, I., Pascal, R., and Kaupp, U.B. (2012). The rate of change in Ca2+ concentration controls sperm chemotaxis. J Cell Biol 196, 653-663.

Kilic, F., Kashikar, N.D., Schmidt, R., Alvarez, L., Dai, L., Weyand, I., Wiesner, B., Goodwin, N., Hagen, V., and Kaupp, U.B. (2009). Caged progesterone: a new tool for studying rapid nongenomic actions of progesterone. J Am Chem Soc 131, 4027-4030.

Alvarez, L. J., Thomen, P., Makushok, T., and Chatenay, D. (2007). Propagation of fluorescent viruses in growing plaques. Biotechnol Bioeng 96, 615-621.


University of Bonn

Neuroscience Master Course:

“Signal Transduction studied with dyes, light-driven proteins, and genetically encoded biosensors”