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?

Publications

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. & 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

Saggiorato, G., Alvarez, L., Jikeli, J., Kaupp, U.B., Gompper, G. & Elgeti, J. (2017) "Human sperm steer with second harmonics of the flagellar beat" Arxiv preprint, 1703.07705

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. & 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. & 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. & Kaupp, U.B. (2015) "A K+-selective CNG channel orchestrates Ca2+ signalling in zebrafish sperm" eLife 4, e07624

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

Strünker, T., Alvarez, L. & 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. & 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. & 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. & Strünker, T. (2014) "Direct action of endocrine disrupting chemicals on human sperm" EMBO Rep., e201438869

Alvarez, L., Friedrich, B.M., Gompper, G. & 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. & 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. & 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. & 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. & 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. & 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. & Chatenay, D. (2007) “Propagation of fluorescent viruses in growing plaques” Biotechnol. Bioeng. 96, 615-621

Teaching

University of Bonn

Neuroscience Master Course:

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