What are the physical constraints and biological implications of molecular fluctuations?
A paradigmatic non-equilibrium system and a remarkable signal transducer
The cells that are responsible for hearing have a mechanoreceptive hair bundle on their apical surface, which gives rise to their name ‘hair cells’. Under physiological conditions these hair bundles display active motility, for which energy has to be transduced. We apply methods from non-equilibrium physics and random dynamical systems theory to characterize and identify the different energy sources for the motility which is key to our remarkable sense of hearing.
The mechanical stimulation of hair cells triggers an electrical signal in the nervous system which involves the activation of voltage-gated calcium channels at specialized synapses. The dynamics of these ion channels has important implications for the signal and noise transduction and the neural coding. To further understand this process I perform patch clamp experiments on dissociated cells.
Related article about the random nonlinear dynamics of bistable oscillations: Phys. Ref. E. (2019)
Related article about myosin Ic, one of the energy sources in hair cells: PLOS Computational Biology (2017)
Top view of spontaneously oscillating hair bundles
From force distributions to molecular mechanisms
Force-spectroscopic methods allow to study the force-dependent interaction of molecules. Molecular motors that convert chemical energy into mechanical energy have a unique coupling of their enzymatic reaction and their force-dependent binding strength to the filament. We develop theoretical methods to analyse data sets from single-molecule experiments to infer the underlying molecular mechanisms. In collaboration with the Gennerich lab, we elucidate the force-dependent structure-function relation of cytoplasmic dynein.
Related article about the regulation of the force-dependent binding strength of cytoplasmic dynein: PNAS (2015)
Robust traffic driven by fluctuating motor molecules
Intracellular transport provides the cell with all kinds of supplies. Different motor molecules are orchestrated to move cargoes around, pull together to generate force, and operate in highly critical processes such as the separation of chromosomes. The dynamics of the single motor molecule is stochastic and force dependent. When they act together, they must be coupled in some way. This coupling in turn determines the function of the molecular ensemble of motor proteins. We study how different motor molecules respond to different coupling and predict their behavior in an ensemble.
In collaboration with experimental colleagues we investigate how transport is regulated by different proteins in the cellular context. As a new line of research, we are also interested in how the network organization of the filaments in different cell types influences the transport and thus regulate the stream of cargo supplies.
Article related to the elastic coupling of processive motors: PRL (2012)
Related article about the regulation of bidirectional transport: Traffic (2017)