Mechanobiology June 26th - June 2nd 2016

Mechanobiology: June 26th  - June 2nd 2016

Niflumic acid disrupts marine spermatozoan chemotaxis without impairing the spatiotemporal detection of chemoattractant gradients
Adán Guerrero, Jesús Espinal, Christopher D. Wood, Juan M. Rendón, Jorge Carneiro, Gustavo Martínez-Mekler, Alberto Darszon


In many broadcast-spawning marine organisms, oocytes release chemicals that guide conspecific spermatozoa towards them through chemotaxis. In the sea urchin Lytechinus pictus, the chemoattractant peptide speract triggers a train of fluctuations of intracellular Ca2+ concentration in the sperm flagella. Each transient Ca2+ elevation leads to a momentary increase in flagellar bending asymmetry, known as a chemotactic turn. Furthermore, chemotaxis requires a precise spatiotemporal coordination between the Ca2+-dependent turns and the form of chemoattractant gradient. Spermatozoa that perform Ca2+-dependent turns while swimming down the chemoattractant gradient, and conversely suppress turning events while swimming up the gradient, successfully approach the center of the gradient. Previous experiments in Strongylocentrotus purpuratus sea urchin spermatozoa showed that niflumic acid (NFA), an inhibitor of several ion channels, drastically altered the speract-induced Ca2+ fluctuations and swimming patterns. In this study, mathematical modeling of the speract-dependent Ca2+ signaling pathway suggests that NFA, by potentially affecting hyperpolarization-activated and cyclic nucleotide-gated channels, Ca2+-regulated Cl channels and/or Ca2+-regulated K+ channels, may alter the temporal organization of Ca2+ fluctuations, and therefore disrupt chemotaxis. We used a novel automated method for analyzing sperm behavior and we identified that NFA does indeed disrupt chemotactic responses of L. pictus spermatozoa, although the temporal coordination between the Ca2+-dependent turns and the form of chemoattractant gradient is unaltered. Instead, NFA disrupts sperm chemotaxis by altering the arc length traveled during each chemotactic turning event. This alteration in the chemotactic turn trajectory disorientates spermatozoa at the termination of the turning event. We conclude that NFA disrupts chemotaxis without affecting how the spermatozoa decode environmental cues.


  • Author contributions

    A.G., A.D. and C.D.W. conceived the project, participated in the design and drafting of the manuscript. A.G. performed the experiments, created the software for the quantitative, automated analysis of sperm chemotaxis and wrote the paper. J.R. supervised the elaboration of the software. J.E., G.M., A.G., A.D. and C.D.W. created the logical model of the speract signaling pathway. J.E., G.M. and J.C. performed the mathematical model calculations and wrote the corresponding section. J.C. supervised, provided advice and contributed to writing the paper. All authors approved the final manuscript.

  • Funding

    This work was supported by Consejo Nacional de Ciencia y Tecnología [grant numbers 49113, 128566 to A.D., 132478 to C.D.W.]; Programa de Apoyo a Proyectos de Investigación e Innovación Technológica [grant number s IN211809, DGAPA/IXTLI IX200910 to A.D., IN223810 to C.D.W., IN109210-F to G.M.]; and Fundação para a Ciência e a Tecnologia [grant number PTDC/SAL-OBD/69928/2006 to J.C.].

  • Supplementary material available online at

  • Accepted December 30, 2012.
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