Dr Maxim Igaev

The integrity and function of our tissues and organs rely on the control of cell division and the precise timing of the underlying cell cycle. A critical aspect of cell division involves the accurate separation of pairs of sister chromosomes in mitosis. To do this, cellular filaments called microtubules bind to each side of a chromosome pair through multiprotein complexes called kinetochores. Microtubules undergo stochastic switches between growth and shortening phases at their ends. By remaining coupled to microtubule ends, kinetochores exploit microtubule polymerisation to transmit forces to the chromosomes.

Fundamental paradoxes at the heart of chromosome segregation are how kinetochores track the ends of microtubules even as they assemble and disassemble and how these ‘fuzzy’ attachments are stabilised under tensile force. This can be imagined as climbing a rope unravelling or being braided underneath one’s hands, while the distance one can climb depends on the amount of applied pulling force. Not an intuitive or particularly enjoyable exercise indeed, but our chromosomes face a similar challenge in every cell cycle.

Our research is driven by the idea that kinetochore-mediated force transduction in yeast mitosis can be understood as a stochastic process in which the kinetochore ‘senses’ the polymerisation state of the microtubule end and selectively stabilises it against spontaneous switches from slow assembly to rapid disassembly. We hypothesise that during chromosome capture and segregation, the kinetochore-microtubule interface undergoes a slip-catch bond transition: force applied to the interface induces conformational changes both in the initially ‘fuzzy’ kinetochore and at the microtubule end that together promote adoption of a highly ordered state with the strongest binding affinity – thus enabling force transmission from the disassembling microtubule to the chromosome. Our aim is to construct the first comprehensive physical model of this attachment in yeast by integrating advanced multiscale simulation approaches with optical and electron microscopy, biochemistry and live cell assays through collaborations at the SLS and worldwide.

Our ultimate goal is to elucidate how evolutionary conserved the kinetochore-microtubule coupling is and whether the same physical principles apply to human kinetochores, potentially transforming our understanding of chromosomal instability and aneuploidy (incorrect number of chromosomes) in cancers. This ambitious goal could thus lead to tailored modulators of spindle mechanochemistry to fight a variety of aneuploid cancer cell types, including those that have become resistant to conventional antimitotic drug therapies.

Selected publications

§ = co-corresponding author, * = co-first author

[1] M Kalutskii, H Grubmüller, V A Volkov§ and M. Igaev§. Microtubule dynamics are defined by conformations and stability of clustered protofilaments. PNAS, 122(22): e2424263122 (2025)

[2] L V Bock, M Igaev and H Grubmüller. Single-particle cryo-EM and molecular dynamics simulations: A perfect match. Curr Opin Struct Biol, 86: 102825 (2024)

[3] M Igaev§ and H Grubmüller§. Bending-torsional elasticity and energetics of the plus-end microtubule tip. PNAS, 119(12): e2115516119 (2022)

[4] M Igaev§ and H Grubmüller§. Microtubule instability driven by longitudinal and lateral strain propagation. PLOS Comp Biol, 16(9): e1008132 (2020)

[5] M Igaev§, C Kutzner, L V Bock, A C Vaiana§ and H Grubmüller§. Automated cryo-EM structure refinement using correlation-driven molecular dynamics. eLife, 8: e43542 (2019)

[6] M Igaev§ and H Grubmüller§. Microtubule assembly governed by tubulin allosteric gain in flexibility and lattice induced fit. eLife, 7: e34353 (2018)

[7] B Niewidok*, M Igaev*, F Sündermann, D Janning, L Bakota and R Brandt. Presence of a carboxyterminal pseudorepeat and disease-like pseudohyperphosphorylation critically influence tau's interaction with microtubules in axon-like processes. Mol Biol Cell, 27(22): 3537-3549 (2016)

[8] M Igaev, D Janning, F Sündermann, B Niewidok, R Brandt and W Junge. A refined reaction-diffusion model of tau-microtubule dynamics and its application in FDAP analysis. Biophys J, 107(11): 2567-2578 (2014)

[9] D Janning*, M Igaev*, F Sündermann, J Brühmann, O Beutel, J J Heinisch, L Bakota, J Piehler, W Junge and R Brandt. Single-molecule tracking of tau reveals fast kiss-and-hop interaction with microtubules in living neurons. Mol Biol Cell, 25(22): 3541-3551 (2014)