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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?
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., DOI:10.15252/embr.201438869
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, DOI: 10.1371/journal.pgen.1003960
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